Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of...Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.展开更多
Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors an...Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.展开更多
Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent art...Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.展开更多
基金supported by the National Natural Science Foundation of China(NSFC)(No.82002312,81972069)supported in part by research grants from the National Institutes of Health,USA(No.CA226303 to TCH,No.DE030480 to RRR)+10 种基金supported by the Science and Technology Research Program of Chongqing Education Commission,China(No.KJQN202100431,KJZD-M202100401)the Top Talent Award from The First Affiliated Hospital of Chongqing Medical University,China(No.BJRC2021-04)Cultivation Program of Postdoctoral Research of The First Affiliated Hospital of Chongqing Medical University,China(No.CYYY-BSHPYXM-202202)supported by a post-doctoral fellowship from Chongqing Medical University and rewarded by China Postdoctoral Science Foundation(No.2022M720605)supported in part by research grants from the 2019 Science and Technology Project of Chongqing Education Commission,China(No.KJQN201900410)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)the Natural Science Foundation of China(No.82102696)supported by the Medical Scientist Training Program of the National Institutes of Health,USA(No.T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant,USA(No.P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health,USA(No.5UL1TR002389)supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopedics Alumni Fund.
文摘Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.
基金supported in part by research grants from the National Institutes of Health(No.CA226303 to TCH and No.DE030480 to RRR)the American Shoulder and Elbow Surgeons PJI Research Grant(LLS).JF was supported in part by research grants from the Natural Science Foundation of China(No.82102696)+4 种基金the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(China)(No.KJQN201900410)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(No.T32 GM007281)This project was also supported in partby The University of Chicago Cancer Center Support Grant(No.P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health through Grant Number 5UL1TR002389.
文摘Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.
基金supported in part by research grants from the National Institutes of Health(No.CA226303 to TCH and No.DE030480 to RRR)supported in part by The University of Chicago Cancer Center Support Grant(No.P30CA014599)+1 种基金the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health(No.5UL1TR002389)TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.Funding sources were not involved in the study design。
文摘Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.
