Long non-coding RNAs(lncRNAs)play a crucial role in normal and dysregulated hematopoiesis.However,the functional repertoire of lncRNAs across various hematopoietic cell types remains elusive.In this study,we construct...Long non-coding RNAs(lncRNAs)play a crucial role in normal and dysregulated hematopoiesis.However,the functional repertoire of lncRNAs across various hematopoietic cell types remains elusive.In this study,we constructed a comprehensive single-cell lncRNA atlas containing 207,113 cells,spanning hematopoietic stem and progenitor cells(HSPCs)to differentiated blood cells,by integrating nine single-cell RNA sequencing(scRNA-seq)datasets derived from 30 healthy donors.The hematopoietic hierarchy based on lncRNA expression was highly consistent with that based on protein-coding genes.We identified 3,463 lineage-specific lncRNAs in HSPCs,neutrophils,monocytes,B cells,and T/natural killer cells;23 of 30 selected lncRNAs were experimentally validated.Importantly,upregulated lncRNAs in pediatric patients with B cell acute lymphoblastic leukemia,T cell acute lymphoblastic leukemia,and acute myeloid leukemia were primarily associated with oxygen response and immune regulation,indicating the potential contribution of lncRNAs to leukemogenesis.In conclusion,our results portray the landscape of lncRNAs in the hematopoietic system,revealing the functional significance of lncRNAs in both normal and abnormal hematopoiesis and providing potential therapeutic targets for the clinical treatment of leukemia.展开更多
Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation,which is crucial for maintaining homeostasis.Acute infections can prompt a hematopoietic response kn...Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation,which is crucial for maintaining homeostasis.Acute infections can prompt a hematopoietic response known as emergency myelopoiesis.In this study,using a Candida albicans(C.albicans)infection model,we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates.Impaired myeloid hematopoiesis and immune cell production were evident,as proved by the decreased numbers of hematopoietic stem and progenitor cells(HSPCs)and granulocytes in the bone marrow of Fhl2-deficient mice.In conclusion,FHL2 regulated emergency myelopoiesis in response to C.albicans,affecting the host’s defense against pathogens.展开更多
The maintenance of hematopoietic stem cells(HSCs)is a complex process involving numerous cell-extrinsic and-intrinsic regulators.The first member of the cyclin-dependent kinase family of inhibitors to be identified,p2...The maintenance of hematopoietic stem cells(HSCs)is a complex process involving numerous cell-extrinsic and-intrinsic regulators.The first member of the cyclin-dependent kinase family of inhibitors to be identified,p21,has been reported to perform a wide range of critical biological functions,including cell cycle regulation,transcription,differentiation,and so on.Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model,we employed p21-tdTomato(tdT)mice to further elucidate its role in HSCs during homeostasis.The results showed that p21-tdT+HSCs exhibited increased self-renewal capacity compared to p21-tdT−HSCs.Zbtb18,a transcriptional repressor,was upregulated in p21-tdT+HSCs,and its knockdown significantly impaired the reconstitution capability of HSCs.Furthermore,p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs.Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.展开更多
Dear Editor,Most cancer cells maintain the length of their telomeres via telomerase(Günes and Rudolph,2013;Kim et al.,1994).However,in some cancers,telomeres are maintained not by telomerase but by alternative le...Dear Editor,Most cancer cells maintain the length of their telomeres via telomerase(Günes and Rudolph,2013;Kim et al.,1994).However,in some cancers,telomeres are maintained not by telomerase but by alternative lengthening of telomeres(Bryan et al.,1997).Telomerase activity appears to be reduced in some bone marrow(BM)diseases,including chronic myeloid leukemia,acute myeloid leukemia(AML),and myeloproliferative neoplasms(MPN),leading to shortened telomeres that correlate with leukemogenesis(Bouillon et al.,2018;Engelhardt et al.,2000;Shay et al.,1996).Our current study aimed to determine the definitive roles of telomeres and telomerase in leukemogenesis.展开更多
基金supported by the National Key Research and Development Program of China(2021YFA1100900 and 2023YFF1204700)the National Natural Science Foundation of China(92368202)+2 种基金the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2021-I2M-1-040)the CAMS Fundamental Research Funds for Central Research Institutes(3332021093)the Haihe Laboratory of Cell Ecosystem Innovation Fund(HH23KYZX0004).
文摘Long non-coding RNAs(lncRNAs)play a crucial role in normal and dysregulated hematopoiesis.However,the functional repertoire of lncRNAs across various hematopoietic cell types remains elusive.In this study,we constructed a comprehensive single-cell lncRNA atlas containing 207,113 cells,spanning hematopoietic stem and progenitor cells(HSPCs)to differentiated blood cells,by integrating nine single-cell RNA sequencing(scRNA-seq)datasets derived from 30 healthy donors.The hematopoietic hierarchy based on lncRNA expression was highly consistent with that based on protein-coding genes.We identified 3,463 lineage-specific lncRNAs in HSPCs,neutrophils,monocytes,B cells,and T/natural killer cells;23 of 30 selected lncRNAs were experimentally validated.Importantly,upregulated lncRNAs in pediatric patients with B cell acute lymphoblastic leukemia,T cell acute lymphoblastic leukemia,and acute myeloid leukemia were primarily associated with oxygen response and immune regulation,indicating the potential contribution of lncRNAs to leukemogenesis.In conclusion,our results portray the landscape of lncRNAs in the hematopoietic system,revealing the functional significance of lncRNAs in both normal and abnormal hematopoiesis and providing potential therapeutic targets for the clinical treatment of leukemia.
基金supported by the National Key Research and Development Program of China(2020YFE0203000,2021YFA1100900)the National Natural Science Foundation of China(92368202,82270120)+2 种基金the Haihe Laboratory of Cell Ecosystem Innovation Fund(22HHXBSS00016)the CAMS Initiative for Innovative Medicine(2021-I2M-1-019,2022-I2M-2-001)the CAMS Fundamental Research Funds for Central Research Institutes(3332021093).
文摘Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation,which is crucial for maintaining homeostasis.Acute infections can prompt a hematopoietic response known as emergency myelopoiesis.In this study,using a Candida albicans(C.albicans)infection model,we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates.Impaired myeloid hematopoiesis and immune cell production were evident,as proved by the decreased numbers of hematopoietic stem and progenitor cells(HSPCs)and granulocytes in the bone marrow of Fhl2-deficient mice.In conclusion,FHL2 regulated emergency myelopoiesis in response to C.albicans,affecting the host’s defense against pathogens.
基金supported by grants from the Ministry of Science and Technology of China(2021YFA1100900,2020YFE0203000,2021YFA1100103)the National Natural Science Foundation of China(92368202,82270120,82222004,82230047)+3 种基金the Haihe Laboratory of Cell Ecosystem Innovation Fund(22HHXBSS00016)the CAMS Initiative for Innovative Medicine(2021-I2M-1-019 and 2022-I2M-2-001)the CAMS Fundamental Research Funds for Central Research Institutes(3332021093)the Distinguished Young Scholars of Tianjin(23JCJQJC00220).
文摘The maintenance of hematopoietic stem cells(HSCs)is a complex process involving numerous cell-extrinsic and-intrinsic regulators.The first member of the cyclin-dependent kinase family of inhibitors to be identified,p21,has been reported to perform a wide range of critical biological functions,including cell cycle regulation,transcription,differentiation,and so on.Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model,we employed p21-tdTomato(tdT)mice to further elucidate its role in HSCs during homeostasis.The results showed that p21-tdT+HSCs exhibited increased self-renewal capacity compared to p21-tdT−HSCs.Zbtb18,a transcriptional repressor,was upregulated in p21-tdT+HSCs,and its knockdown significantly impaired the reconstitution capability of HSCs.Furthermore,p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs.Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
基金supported by the National Key Research and Development Program of China(2016YFA0100600,2017YFA0103400)the National Natural Science Foundation of China(81421002,81730006,81430004,81870086,8181101081)+1 种基金CAMS Initiative for Innovative Medicine(2017-I2M-3-009,2016-I2M-1-017)the CAMS Fundamental Research Funds for Central Research Institutes(2018PT31005)。
文摘Dear Editor,Most cancer cells maintain the length of their telomeres via telomerase(Günes and Rudolph,2013;Kim et al.,1994).However,in some cancers,telomeres are maintained not by telomerase but by alternative lengthening of telomeres(Bryan et al.,1997).Telomerase activity appears to be reduced in some bone marrow(BM)diseases,including chronic myeloid leukemia,acute myeloid leukemia(AML),and myeloproliferative neoplasms(MPN),leading to shortened telomeres that correlate with leukemogenesis(Bouillon et al.,2018;Engelhardt et al.,2000;Shay et al.,1996).Our current study aimed to determine the definitive roles of telomeres and telomerase in leukemogenesis.
