Extragonadal germ cell tumors are rare. The most common sites for EGGCTs are in midline locations such as the mediastinum, retroperitoneum and pineal gland. These tumors rarely present in the stomach. We describe here...Extragonadal germ cell tumors are rare. The most common sites for EGGCTs are in midline locations such as the mediastinum, retroperitoneum and pineal gland. These tumors rarely present in the stomach. We describe here a case where a middle aged man presented with typical symptoms of gastric cancer. After extensive workup, which included blood work, CT abdomen scan, upper endoscopy, and endoscopic ultrasound, the patient was diagnosed with gastric cancer. However, due to very high blood levels of alpha-fetoprotein, the specimen was sent for special histochemical staining, which demonstrated that the tumor had features of both adenocarcinoma and endodermal sinus tumor. This is a very aggressive tumor with a very poor prognosis.展开更多
Objective To clarify the clinical features,therapeutic method and outcomes of the primary endodermal sinus tumors(ESTs)in the posterior cranial fossa.Methods The English literatures on EST in the posterior cranial fos...Objective To clarify the clinical features,therapeutic method and outcomes of the primary endodermal sinus tumors(ESTs)in the posterior cranial fossa.Methods The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed.And a 4-year-old boy diagnosed with EST in our hospital was reported.The clinical manifestations,therapy,pathologic features,and prognosis of these cases were analyzed.Results Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review,including six cases searched from the PubMed and one case from our hospital.Six patients were boy and one patient’s gender was not available from the report.Ages ranged from 1 to 5 years(mean 3.14 years).The mean tumor size in our cohort was 4.4 cm.Six cases came from East Asia.Schiller-Duval bodies were found in all seven neoplasms.All tumors were positive for alpha-fetoprotein.The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy.The mean follow-up time was 24.4 months(range 5-52 months).Six tumors were totally removed,and four of them recurred.Three cases died including one whose tumor was partially removed.Conclusions The serum alpha-fetoprotein level is well correlated with the severity of the tumor.A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa.The prognosis of extragonadal intracranial EST is poor.展开更多
BACKGROUND Endodermal sinus tumors(ESTs),which arise primarily in children and adolescents,account for 20%of malignant ovarian germ cell tumors,but constitute only 1%of all ovarian malignancies.Treatment of ESTs consi...BACKGROUND Endodermal sinus tumors(ESTs),which arise primarily in children and adolescents,account for 20%of malignant ovarian germ cell tumors,but constitute only 1%of all ovarian malignancies.Treatment of ESTs consists of surgical staging with fertility-sparing surgery and chemotherapy.CASE SUMMARY A 15-year-old nulliparous patient was diagnosed with disseminated ovarian ESTs after laparoscopic unilateral salpingo-oophorectomy using uncontained power morcellation for treatment of a ruptured solid adnexal mass in another hospital.Exploratory laparotomy;total abdominal hysterectomy,right salpingooophorectomy,and lymphadenectomy were performed with optimal debulking,and surgical stage 3C was assigned to the patient.CONCLUSION In 2014,the Food and Drug Administration noted that power morcellation was probably associated with a risk of disseminating suspected cancerous tissue.Furthermore,the use of power morcellation to remove solid adnexal mass is considered a contraindication because of the potential for a malignant tumor.This case report aims to warn of the dangers of using uncontained power morcellation to treat solid adnexal masses.展开更多
Case Report An female infant patient, aged 8 months old, suffered from irregular colporrhagia for a period of 1 month after which she was taken to our hospital on 30th April, 2003. A pelvic CT examination displayed a ...Case Report An female infant patient, aged 8 months old, suffered from irregular colporrhagia for a period of 1 month after which she was taken to our hospital on 30th April, 2003. A pelvic CT examination displayed a 6.5 cm×3.0 cm shadow of a soft-tissue tumor growing longitudinally in her supravaginal uterine area （Fig. 1）. The density of the shadow was uneven, in which there were irregular low-density loci, an indication of a compression of the colon and bladder and a diffuse boundary between the posterior wall of the urinary bladder and tumor. No abnormalities were found in either kidney or ovary, the liver or gall bladder. Also no obvious lesions were seen on the chest X-ray film, and routine blood and urine laboratory examinations were normal.展开更多
A 10-year-old boy appeared with a headache, mainly in the forehead, and with lethargy at noon on November 10, 2004. He reported discontinuous gas pains, no nausea, no vomiting and no blurred vision. He thought that he...A 10-year-old boy appeared with a headache, mainly in the forehead, and with lethargy at noon on November 10, 2004. He reported discontinuous gas pains, no nausea, no vomiting and no blurred vision. He thought that he had a ＂common cold＂, but treatment for 3 days produced no result. He was diagnosed as having viral encephalitis after an examination including an electroencephalogram （EEG）, blood biochemistry and lumbar puncture, etc. in a local hospital on November 15. After further treatment for 3 days his symptoms became aggravated showing instability of gait and involuntary movement of his head and extremities. Cranial CT showed： a 4.0 cm×4.0 cm×5.0 cm lump in the cerebellar vermis which intruded into the fourth ventricle inducing evident distention of the third and lateral ventricle. He was diagnosed with blastoma of the cerebellum.展开更多
Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of variou...Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases.In this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic organoids.We also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this technology.Finally,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.展开更多
Liver is one of the largest internal organs in the body and its importance for metabolism, detoxification and homeostasis has been well established. In this review, we summarized recent progresses in studying liver in...Liver is one of the largest internal organs in the body and its importance for metabolism, detoxification and homeostasis has been well established. In this review, we summarized recent progresses in studying liver initiation and development during embryogenesis using zebrafish as a model system. We mainly focused on topics related to the specification of hepatoblasts from endoderm, the formation and growth of liver bud, the differentiation of hepatocytes and bile duct cells from hepatoblasts, and finally the role of mesodermal signals in controlling liver development in zebrafish.展开更多
Embryonic stem （ES） cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy...Embryonic stem （ES） cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy. ES cells of mouse and human have been successfully generated and applied in a wide range of research. However, no genuine ES cell lines have been obtained from rat to date. In this study, we identified pluripotent cells in early rat embryos using specific antibodies against markers of pluripotent stem ceils. Subsequently, by modifying the culture medium for rat blastocysts, we derived pluripotent rat ES-like cell lines, which expressed pluripotency markers and formed embryoid bodies （EBs） in vitro. Importantly, these rat ES-like cells were able to produce teratomas. Both EBs and teratomas contained tissues from all three embryonic germ layers. In addition, from the rat ES-like cells, we derived a rat primitive endoderm （PrE） cell line. Furthermore, we conducted transcriptional profiling of the rat ES-like cells and identified the unique molecular signature of the rat pluripotent stem cells. Our analysis demonstrates that multiple signaling pathways, including the BMP, Activin and mTOR pathways, may be involved in keeping the rat ES-like cells in an undifferentiated state. The cell lines and information obtained in this study will accelerate our understanding of the molecular regulation underlying pluripotency and guide us in the appropriate manipulation of ES cells from a particular species.展开更多
Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the ide...Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.展开更多
Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem （ES） cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line...Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem （ES） cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line is a well-documented model system for endoderm cell lineage differentiation. Here, we examined the function of Nanog in F9 cell endoderm differentiation. Over-expression of Nanog returns the F9 cells to the early status of ES cells and represses the differentiation of primitive endoderm and parietal endoderm in F9 cells, whereas it has no effect on the differentiation of visceral endoderm. In contrast, the expression of C-terminal domain-truncated Nanog spontaneously promotes endoderm differentiation in F9 cells. These data suggest that Nanog is required to sustain the proper undifferentiated status of F9 cells, and the C-terminal domain of Nanog transduces the most effects in repressing primitive endoderm and parietal endoderm differentiation in F9 cells.展开更多
Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment,yet their origins and underlying mechanisms remain uncertain.Here,we conduct a detailed investigation of sex di...Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment,yet their origins and underlying mechanisms remain uncertain.Here,we conduct a detailed investigation of sex differences in human pre-gastrulation embryos.The lower methylation and incomplete inactivation of the X chromosome in females,as well as the sex-specific cell-cell communication patterns,contribute to sex-differential transcription.Male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity,while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals.Male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females.The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females,while the situation is opposite in the trophectoderm.In conclusion,our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.展开更多
Accumulated studies have demonstrated that long noncoding RNAs(lncRNAs)play crucial regulatory roles in diverse biological processes,such as embryonic development and cell diferentiation.Comprehensive transcriptome an...Accumulated studies have demonstrated that long noncoding RNAs(lncRNAs)play crucial regulatory roles in diverse biological processes,such as embryonic development and cell diferentiation.Comprehensive transcriptome analysis identifes extensive lncRNAs,gradually elucidating their functions across various contexts.Recent studies have highlighted the essential role of lncRNAs in defnitive endoderm diferentiation,underscoring their importance in early development.In this review,we have analyzed the features of overlapping,proximal,and desert lncRNAs,classifed by genomic location,in pluripotent stem cells(PSCs)and the diferentiation derivatives.Furthermore,we focus on the endoderm lineage and review the latest advancements in lncRNA identifcation and their distinct regulatory mechanisms.By consolidating current knowledge,we aim to provide a clearer perspective on how lncRNAs contribute to endoderm diferentiation in diferent manners.展开更多
Development of animal embryos before zygotic genome activation at the mid blastula transition （MBT） is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endod...Development of animal embryos before zygotic genome activation at the mid blastula transition （MBT） is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrotateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a （Eomesa）, a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2, a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2, and rnxtx2 to activate their transcrip- tion. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved rote of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos.展开更多
Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation d...Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.展开更多
Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Ki...Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.展开更多
文摘Extragonadal germ cell tumors are rare. The most common sites for EGGCTs are in midline locations such as the mediastinum, retroperitoneum and pineal gland. These tumors rarely present in the stomach. We describe here a case where a middle aged man presented with typical symptoms of gastric cancer. After extensive workup, which included blood work, CT abdomen scan, upper endoscopy, and endoscopic ultrasound, the patient was diagnosed with gastric cancer. However, due to very high blood levels of alpha-fetoprotein, the specimen was sent for special histochemical staining, which demonstrated that the tumor had features of both adenocarcinoma and endodermal sinus tumor. This is a very aggressive tumor with a very poor prognosis.
文摘Objective To clarify the clinical features,therapeutic method and outcomes of the primary endodermal sinus tumors(ESTs)in the posterior cranial fossa.Methods The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed.And a 4-year-old boy diagnosed with EST in our hospital was reported.The clinical manifestations,therapy,pathologic features,and prognosis of these cases were analyzed.Results Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review,including six cases searched from the PubMed and one case from our hospital.Six patients were boy and one patient’s gender was not available from the report.Ages ranged from 1 to 5 years(mean 3.14 years).The mean tumor size in our cohort was 4.4 cm.Six cases came from East Asia.Schiller-Duval bodies were found in all seven neoplasms.All tumors were positive for alpha-fetoprotein.The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy.The mean follow-up time was 24.4 months(range 5-52 months).Six tumors were totally removed,and four of them recurred.Three cases died including one whose tumor was partially removed.Conclusions The serum alpha-fetoprotein level is well correlated with the severity of the tumor.A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa.The prognosis of extragonadal intracranial EST is poor.
文摘BACKGROUND Endodermal sinus tumors(ESTs),which arise primarily in children and adolescents,account for 20%of malignant ovarian germ cell tumors,but constitute only 1%of all ovarian malignancies.Treatment of ESTs consists of surgical staging with fertility-sparing surgery and chemotherapy.CASE SUMMARY A 15-year-old nulliparous patient was diagnosed with disseminated ovarian ESTs after laparoscopic unilateral salpingo-oophorectomy using uncontained power morcellation for treatment of a ruptured solid adnexal mass in another hospital.Exploratory laparotomy;total abdominal hysterectomy,right salpingooophorectomy,and lymphadenectomy were performed with optimal debulking,and surgical stage 3C was assigned to the patient.CONCLUSION In 2014,the Food and Drug Administration noted that power morcellation was probably associated with a risk of disseminating suspected cancerous tissue.Furthermore,the use of power morcellation to remove solid adnexal mass is considered a contraindication because of the potential for a malignant tumor.This case report aims to warn of the dangers of using uncontained power morcellation to treat solid adnexal masses.
文摘Case Report An female infant patient, aged 8 months old, suffered from irregular colporrhagia for a period of 1 month after which she was taken to our hospital on 30th April, 2003. A pelvic CT examination displayed a 6.5 cm×3.0 cm shadow of a soft-tissue tumor growing longitudinally in her supravaginal uterine area （Fig. 1）. The density of the shadow was uneven, in which there were irregular low-density loci, an indication of a compression of the colon and bladder and a diffuse boundary between the posterior wall of the urinary bladder and tumor. No abnormalities were found in either kidney or ovary, the liver or gall bladder. Also no obvious lesions were seen on the chest X-ray film, and routine blood and urine laboratory examinations were normal.
文摘A 10-year-old boy appeared with a headache, mainly in the forehead, and with lethargy at noon on November 10, 2004. He reported discontinuous gas pains, no nausea, no vomiting and no blurred vision. He thought that he had a ＂common cold＂, but treatment for 3 days produced no result. He was diagnosed as having viral encephalitis after an examination including an electroencephalogram （EEG）, blood biochemistry and lumbar puncture, etc. in a local hospital on November 15. After further treatment for 3 days his symptoms became aggravated showing instability of gait and involuntary movement of his head and extremities. Cranial CT showed： a 4.0 cm×4.0 cm×5.0 cm lump in the cerebellar vermis which intruded into the fourth ventricle inducing evident distention of the third and lateral ventricle. He was diagnosed with blastoma of the cerebellum.
文摘Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases.In this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic organoids.We also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this technology.Finally,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.
基金supported by the National Natural Science Foundation of China (No. 30825025)
文摘Liver is one of the largest internal organs in the body and its importance for metabolism, detoxification and homeostasis has been well established. In this review, we summarized recent progresses in studying liver initiation and development during embryogenesis using zebrafish as a model system. We mainly focused on topics related to the specification of hepatoblasts from endoderm, the formation and growth of liver bud, the differentiation of hepatocytes and bile duct cells from hepatoblasts, and finally the role of mesodermal signals in controlling liver development in zebrafish.
文摘Embryonic stem （ES） cells are derived from blastocyst-stage embryos. Their unique properties of self-renewal and pluripotency make them an attractive tool for basic research and a potential cell resource for therapy. ES cells of mouse and human have been successfully generated and applied in a wide range of research. However, no genuine ES cell lines have been obtained from rat to date. In this study, we identified pluripotent cells in early rat embryos using specific antibodies against markers of pluripotent stem ceils. Subsequently, by modifying the culture medium for rat blastocysts, we derived pluripotent rat ES-like cell lines, which expressed pluripotency markers and formed embryoid bodies （EBs） in vitro. Importantly, these rat ES-like cells were able to produce teratomas. Both EBs and teratomas contained tissues from all three embryonic germ layers. In addition, from the rat ES-like cells, we derived a rat primitive endoderm （PrE） cell line. Furthermore, we conducted transcriptional profiling of the rat ES-like cells and identified the unique molecular signature of the rat pluripotent stem cells. Our analysis demonstrates that multiple signaling pathways, including the BMP, Activin and mTOR pathways, may be involved in keeping the rat ES-like cells in an undifferentiated state. The cell lines and information obtained in this study will accelerate our understanding of the molecular regulation underlying pluripotency and guide us in the appropriate manipulation of ES cells from a particular species.
基金Supported by the Korea Health Technology RD Project through the Korea Health Industry Development Institutethe Ministry of Health and Welfare,No.HI16C-2207+1 种基金the Basic Science Research Program through the NRF,No.NRF-2018R1D1A1A09083264Ewha Womans University,No.RP-grant2017
文摘Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.
文摘Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem （ES） cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line is a well-documented model system for endoderm cell lineage differentiation. Here, we examined the function of Nanog in F9 cell endoderm differentiation. Over-expression of Nanog returns the F9 cells to the early status of ES cells and represses the differentiation of primitive endoderm and parietal endoderm in F9 cells, whereas it has no effect on the differentiation of visceral endoderm. In contrast, the expression of C-terminal domain-truncated Nanog spontaneously promotes endoderm differentiation in F9 cells. These data suggest that Nanog is required to sustain the proper undifferentiated status of F9 cells, and the C-terminal domain of Nanog transduces the most effects in repressing primitive endoderm and parietal endoderm differentiation in F9 cells.
基金funded by grants from the National Key Research and Development Program(2019YFA0110001 and 2022YFC2702200)the National Natural Science Foundation of China(82288102,82125013,82201838,and 82101677)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20200398)。
文摘Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment,yet their origins and underlying mechanisms remain uncertain.Here,we conduct a detailed investigation of sex differences in human pre-gastrulation embryos.The lower methylation and incomplete inactivation of the X chromosome in females,as well as the sex-specific cell-cell communication patterns,contribute to sex-differential transcription.Male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity,while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals.Male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females.The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females,while the situation is opposite in the trophectoderm.In conclusion,our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.
基金supported by the National Natural Science Foundation of China(No.32270857)the Wuhan Intellectual Innovation Fund(2023020201010074)+1 种基金the Open Funds of Hubei Key Laboratory of Embryonic Stem Cell Research(Hubei University of Medicine)(ESOF2023003)the Fundamental Research Funds for the Central Universities in China(2042022dx0003).
文摘Accumulated studies have demonstrated that long noncoding RNAs(lncRNAs)play crucial regulatory roles in diverse biological processes,such as embryonic development and cell diferentiation.Comprehensive transcriptome analysis identifes extensive lncRNAs,gradually elucidating their functions across various contexts.Recent studies have highlighted the essential role of lncRNAs in defnitive endoderm diferentiation,underscoring their importance in early development.In this review,we have analyzed the features of overlapping,proximal,and desert lncRNAs,classifed by genomic location,in pluripotent stem cells(PSCs)and the diferentiation derivatives.Furthermore,we focus on the endoderm lineage and review the latest advancements in lncRNA identifcation and their distinct regulatory mechanisms.By consolidating current knowledge,we aim to provide a clearer perspective on how lncRNAs contribute to endoderm diferentiation in diferent manners.
基金Acknowledgements We thank Drs Alex Schier and Susan Mango （Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA） for discussion and suggestions, Dr David Kimelman （Department of Biochemistry, University of Washington, Seattle, WA, USA） for myc-eomesa construct, and members of the Meng lab for discussion and technical assistance. This work was financially supported by grants from the Major Science Research Programs of China （2011CB943800） and the National Natural Science Foundation of China （31221064）.
文摘Development of animal embryos before zygotic genome activation at the mid blastula transition （MBT） is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrotateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a （Eomesa）, a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2, a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2, and rnxtx2 to activate their transcrip- tion. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved rote of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos.
基金supported by the National Key R&D Program of China(Nos.2020YFA0112500 and 2021YFA1102900)the National Natural Science Foundation of China(Nos.31721003,81630035,82022027,31871448,32000418 and 31820103009)+2 种基金supported by the key project of the Science and Technology of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500)the Shanghai municipal medical and health discipline construction projects(No.2017ZZ02015)the China Postdoctoral Science Foundation 2021M692437 and the Fundamental Research Funds for the Central Universities.
文摘Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
基金supported by the National Natural Science Foundation of China(81301802,81230051,30830048,31170711)Grant of Ministry of Science and Technology of China(2013CB910501,2010CB912203,2010CB529402)+3 种基金Program for Introducing Talents of Discipline to Universities(111 Project)of Ministry of EducationBeijing Natural Science Foundation(7120002)Peking University grants(BMU20120314,BMU20130364,BMU20130373)a Leading Academic Discipline Project of Beijing Education Bureau
文摘Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.
