Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoid...Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoidof any Hox gene expression, but these transcription factors are activated in varying spatial and temporal patterns defining the development of various body regions. In the adult body, Hox genes are among others responsible for driving the differentiation of tissue stem cells towards their respective lineages in order to repair and maintain the correct function of tissues and organs. Due to their involvement in the embryonic and adult body, they have been suggested to be useable for improving stem cell differentiations in vitro and in vivo. In many studies Hox genes have been found as driving factors in stem cell differentiation towards adipogenesis, in lineages involved in bone and joint formation, mainly chondrogenesis and osteogenesis, in cardiovascular lineages including endothelial and smooth muscle cell differentiations, and in neurogenesis. As life expectancy is rising, the demand for tissue reconstruction continues to increase. Stem cells have become an increasingly popular choice for creating therapies in regenerative medicine due to their self-renewal and differentiation potential. Especially mesenchymal stem cells are used more and more frequently due to their easy handling and accessibility, combined with a low tumorgenicity and little ethical concerns. This review therefore intends to summarize to date known correlations between natural Hox gene expression patterns in body tissues and during the differentiation of various stem cells towards their respective lineages with a major focus on mesenchymal stem cell differentiations. This overview shall help to understand the complex interactions of Hox genes and differentiation processes all over the body as well as in vitro for further improvement of stem cell treatments in future regenerative medicine approaches.展开更多
Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not ...Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem cells.Recent studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and disease.These investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time points.Furthermore,recent studies have shed light on the characteristics of ssCs in both physiological and pathological conditions.This review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.展开更多
The lung is the most critical organ of the respiratory system supporting gas exchange.Constant interaction with the external environment makes the lung vulnerable to injury.Thus,a deeper understanding of cellular and ...The lung is the most critical organ of the respiratory system supporting gas exchange.Constant interaction with the external environment makes the lung vulnerable to injury.Thus,a deeper understanding of cellular and molecular processes underlying lung development programs and evaluation of progenitor status within the lung is an essential part of lung regenerative medicine.In this review,we aim to discuss the current understanding of lung development process and regenerative capability.We highlight the advances brought by multi-omics approaches,single-cell transcriptome,in particular,that can help us further dissect the cellular player and molecular signaling underlying those processes.展开更多
MADM （Mosaic Analysis with Double Markers） technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cr...MADM （Mosaic Analysis with Double Markers） technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes--green GFP and red tdTomato -- and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.展开更多
In the mammalian central nervous system,nerve-glia antigen 2(NG2)glia are considered the fourth glial population in addition to astrocytes,oligodendrocytes and microglia.The fate of NG2 glia in vivo has been carefully...In the mammalian central nervous system,nerve-glia antigen 2(NG2)glia are considered the fourth glial population in addition to astrocytes,oligodendrocytes and microglia.The fate of NG2 glia in vivo has been carefully studied in several transgenic mouse models using the Cre/loxP strategy.There is a clear agreement that NG2 glia mainly serve as progenitors for oligodendrocytes and a subpopulation of astrocytes mainly in the ventral forebrain,whereas the existence of a neurogenic potential of NG2 glia is lack of adequate evidence.This mini review summarizes the findings from recent studies regarding the fate of NG2 glia during development.We will highlight the age-and-region-dependent heterogeneity of the NG2 glia differentiation potential.We will also discuss putative reasons for inconsistent findings in various transgenic mouse lines of previous studies.展开更多
基金BMBF,Adi Pa D,1720X06,BMBF,FHprof Unt,FKZ:03FH012PB2FH-Extra,"Europischer Fonds für regionale Entwicklung","Europa-Investition in unsere Zukunft",FKZ:z1112fh012EFRE co-financed NRW Ziel 2:"Regionale Wettbewerbsfhigkeit und Beschftigung",DAAD,PPP Vigoni,FKZ:314-vigoni-dr and FKZ:54669218 for Edda Tobiasch
文摘Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoidof any Hox gene expression, but these transcription factors are activated in varying spatial and temporal patterns defining the development of various body regions. In the adult body, Hox genes are among others responsible for driving the differentiation of tissue stem cells towards their respective lineages in order to repair and maintain the correct function of tissues and organs. Due to their involvement in the embryonic and adult body, they have been suggested to be useable for improving stem cell differentiations in vitro and in vivo. In many studies Hox genes have been found as driving factors in stem cell differentiation towards adipogenesis, in lineages involved in bone and joint formation, mainly chondrogenesis and osteogenesis, in cardiovascular lineages including endothelial and smooth muscle cell differentiations, and in neurogenesis. As life expectancy is rising, the demand for tissue reconstruction continues to increase. Stem cells have become an increasingly popular choice for creating therapies in regenerative medicine due to their self-renewal and differentiation potential. Especially mesenchymal stem cells are used more and more frequently due to their easy handling and accessibility, combined with a low tumorgenicity and little ethical concerns. This review therefore intends to summarize to date known correlations between natural Hox gene expression patterns in body tissues and during the differentiation of various stem cells towards their respective lineages with a major focus on mesenchymal stem cell differentiations. This overview shall help to understand the complex interactions of Hox genes and differentiation processes all over the body as well as in vitro for further improvement of stem cell treatments in future regenerative medicine approaches.
基金supported in part by National Natural Science Foundation of China(Grant nos.82372362,81972034,92068104 to Ren Xu and 82002262 to Na Li)National Key R&D Program of China(2020YFA0112900 to Ren Xu)+2 种基金Natural Science Foundation of Fujian Province(2022J06003 to Ren Xu)Project of Xiarmen Cell Therapy Research,Xiamen,Fujian,China(3502Z20214001)supported by a Pershing Square MIND Prize award,an Irma T.Hirschl Career Scientist Award,an NIH award RO1AR075585,a Career Award for Medical Scientists from the Burroughs Welcome Foundation,a William Rhodes and Louise Tilzer-Rhodes Center for Glioblastoma research award,and a Weill Comell Medicine Prostate Cancer SPORE Developmental Research Program Award。
文摘Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem cells.Recent studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and disease.These investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time points.Furthermore,recent studies have shed light on the characteristics of ssCs in both physiological and pathological conditions.This review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.
基金supported by Science and Technology Planning Project of Guangdong Province(2020B1212060052)supported by Guangdong Basic and Applied Basic Research Foundation(2019A1515110985).
文摘The lung is the most critical organ of the respiratory system supporting gas exchange.Constant interaction with the external environment makes the lung vulnerable to injury.Thus,a deeper understanding of cellular and molecular processes underlying lung development programs and evaluation of progenitor status within the lung is an essential part of lung regenerative medicine.In this review,we aim to discuss the current understanding of lung development process and regenerative capability.We highlight the advances brought by multi-omics approaches,single-cell transcriptome,in particular,that can help us further dissect the cellular player and molecular signaling underlying those processes.
文摘MADM （Mosaic Analysis with Double Markers） technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes--green GFP and red tdTomato -- and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.
基金This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG Sino-German joint project(Kl 503/14-1)to WH,DFG FOR 2289 to ASfrom the Saarland University Medical Faculty HOMFOR2015 and HOMFORexzellenz2016 to AS and WH,respectivelyWH was also supported by DFG SFB 894 and the European Commission EC-H2020 FET ProAct Neurofibres.
文摘In the mammalian central nervous system,nerve-glia antigen 2(NG2)glia are considered the fourth glial population in addition to astrocytes,oligodendrocytes and microglia.The fate of NG2 glia in vivo has been carefully studied in several transgenic mouse models using the Cre/loxP strategy.There is a clear agreement that NG2 glia mainly serve as progenitors for oligodendrocytes and a subpopulation of astrocytes mainly in the ventral forebrain,whereas the existence of a neurogenic potential of NG2 glia is lack of adequate evidence.This mini review summarizes the findings from recent studies regarding the fate of NG2 glia during development.We will highlight the age-and-region-dependent heterogeneity of the NG2 glia differentiation potential.We will also discuss putative reasons for inconsistent findings in various transgenic mouse lines of previous studies.
