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
The development of the mammalian neocortex involves rounds of symmetric and asymmetric cell division of neural progenitors to fulfill needs of both self-renewal of progenitors and production of differentiated progenie...The development of the mammalian neocortex involves rounds of symmetric and asymmetric cell division of neural progenitors to fulfill needs of both self-renewal of progenitors and production of differentiated progenies such as neurons and glia. The machinery for asymmetric cell division is evolutionarily conserved and extensively used in organogeuesis and homeostasis of adult tissues. Here we summarize recent progress regarding cellular characteristics of different types of neural progenitors in mammals, highlighting how asymmetric cell division is utilized during cortical development.展开更多
Asymmetric cell division(ACD) is a fundamental process that generates new cell types during development in eukaryotic species.In plant development,post-embryonic organogenesis driven by ACD is universal and more impor...Asymmetric cell division(ACD) is a fundamental process that generates new cell types during development in eukaryotic species.In plant development,post-embryonic organogenesis driven by ACD is universal and more important than in animals,in which organ pattern is preset during embryogenesis.Thus,plant development provides a powerful system to study molecular mechanisms underlying ACD.During the past decade,tremendous progress has been made in our understanding of the key components and mechanisms involved in this important process in plants.Here,we present an overview of how ACD is determined and regulated in multiple biological processes in plant development and compare their conservation and specificity among different model cell systems.We also summarize the molecular roles and mechanisms of the phytohormones in the regulation of plant ACD.Finally,we conclude with the overarching paradigms and principles that govern plant ACD and consider how new technologies can be exploited to fill the knowledge gaps and make new advances in the field.展开更多
Chromophore-assisted laser inactivation（CALI） is a technique that uses photochemically-generated reactive oxygen species to acutely inactivate target proteins in living cells.Neural development includes highly dynam...Chromophore-assisted laser inactivation（CALI） is a technique that uses photochemically-generated reactive oxygen species to acutely inactivate target proteins in living cells.Neural development includes highly dynamic cellular processes such as asymmetric cell division,migration,axon and dendrite outgrowth and synaptogenesis.Although many key molecules of neural development have been identified since the past decades,their spatiotemporal contributions to these cellular events are not well understood.CALI provides an appealing tool for elucidating the precise functions of these molecules during neural development.In this review,we summarize the principles of CALI,a recent microscopic setup to perform CALI experiments,and the application of CALI to the study of growth-cone motility and neuroblast asymmetric division.展开更多
Cell polarization and asymmetric cell divisions play important roles during development in many multicellular eukaryotes. Fucoid algae have a long history as models for studying early developmental processes, probably...Cell polarization and asymmetric cell divisions play important roles during development in many multicellular eukaryotes. Fucoid algae have a long history as models for studying early developmental processes, probably because of the ease with which zygotes can be observed and manipulated in the laboratory. This review discusses cell polarization and asymmetric cell divisions in fucoid algal zygotes with an emphasis on the roles played by the cytoskeleton.展开更多
Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more dif...Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate the tissue. During asymmetric cell division, protein cell fate determinants asymmetrically localize to the opposite poles of a dividing cell to cause distinct cell fate. However, it remains unclear whether cell fate determination is robust to fluctuations and noise during this spatial allocation process. To answer this question, we engineered Caulobacter, a bacterial model for asymmetric division, to express synthetic scaffolds with modular protein interaction domains. These scaffolds perturbed the spatial distribution of the PleC-DivJ- DivK phospho-signaling network without changing their endogenous expression levels. Surprisingly, enforcing symmetrical distribution of these cell fate de terminants did not result in symmetric daughter fate or any morphological defects. Further computational analysis suggested that PleC and DivJ form a robust phospho-switch that can tolerate high amount of spatial variation. This insight may shed light on the presence of similar phospho-switches in stem cell asymmetric division regulation. Overall, our study demonstrates that synthetic protein scaffolds can provide a useful tool to probe biological systems for better understanding of their operating principles.展开更多
Adaptation allows organisms to maintain a constant internal environment,which is optimised for growth.The unfolded protein response(UPR)is an example of a feedback loop that maintains endoplasmic reticulum(ER)homeosta...Adaptation allows organisms to maintain a constant internal environment,which is optimised for growth.The unfolded protein response(UPR)is an example of a feedback loop that maintains endoplasmic reticulum(ER)homeostasis,and is characteristic of how adaptation is often mediated by transcriptional networks.The more recent discovery of asymmetric division in maintaining ER homeostasis,however,is an example of how alternative non-transcriptional pathways can exist,but are overlooked by gold standard transcriptomic or proteomic population-based assays.In this study,we have used a combination of fluorescent reporters,flow cytometry and mathematical modelling to explore the relative roles of asymmetric cell division and the UPR in maintaining ER homeostasis.Under low ER stress,asymmetric division leaves daughter cells with an ER deficiency,necessitating activation of the UPR and prolonged cell cycle during which they can recover ER functionality before growth.Mathematical analysis of and simulation results from our mathematical model reinforce the experimental observations that low ER stress primarily impacts the growth rate of the daughter cells.These results demonstrate the interplay between homeostatic pathways and the importance of exploring sub-population dynamics to understand population adaptation to quantitatively different stresses.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.
文摘The development of the mammalian neocortex involves rounds of symmetric and asymmetric cell division of neural progenitors to fulfill needs of both self-renewal of progenitors and production of differentiated progenies such as neurons and glia. The machinery for asymmetric cell division is evolutionarily conserved and extensively used in organogeuesis and homeostasis of adult tissues. Here we summarize recent progress regarding cellular characteristics of different types of neural progenitors in mammals, highlighting how asymmetric cell division is utilized during cortical development.
基金supported by grants from the National Natural Science Foundation of China (grant nos.32130010,31422008) to T.X.the National Institute of Health (grant no.GM131827)the National Science Foundation (grant nos.1851907,1952823,and 2049642) to J.D。
文摘Asymmetric cell division(ACD) is a fundamental process that generates new cell types during development in eukaryotic species.In plant development,post-embryonic organogenesis driven by ACD is universal and more important than in animals,in which organ pattern is preset during embryogenesis.Thus,plant development provides a powerful system to study molecular mechanisms underlying ACD.During the past decade,tremendous progress has been made in our understanding of the key components and mechanisms involved in this important process in plants.Here,we present an overview of how ACD is determined and regulated in multiple biological processes in plant development and compare their conservation and specificity among different model cell systems.We also summarize the molecular roles and mechanisms of the phytohormones in the regulation of plant ACD.Finally,we conclude with the overarching paradigms and principles that govern plant ACD and consider how new technologies can be exploited to fill the knowledge gaps and make new advances in the field.
基金supported by grants from the National Basic Research Program of China (973 Program) to W.L.and G.O.(2012CB966800 and 2012CB945002)the National Natural Science Foundation of China to W.L.and G.O.(31101002,31171295 and 31190063)the Junior Thousand Talents Program of China to G.O
文摘Chromophore-assisted laser inactivation（CALI） is a technique that uses photochemically-generated reactive oxygen species to acutely inactivate target proteins in living cells.Neural development includes highly dynamic cellular processes such as asymmetric cell division,migration,axon and dendrite outgrowth and synaptogenesis.Although many key molecules of neural development have been identified since the past decades,their spatiotemporal contributions to these cellular events are not well understood.CALI provides an appealing tool for elucidating the precise functions of these molecules during neural development.In this review,we summarize the principles of CALI,a recent microscopic setup to perform CALI experiments,and the application of CALI to the study of growth-cone motility and neuroblast asymmetric division.
文摘Cell polarization and asymmetric cell divisions play important roles during development in many multicellular eukaryotes. Fucoid algae have a long history as models for studying early developmental processes, probably because of the ease with which zygotes can be observed and manipulated in the laboratory. This review discusses cell polarization and asymmetric cell divisions in fucoid algal zygotes with an emphasis on the roles played by the cytoskeleton.
文摘Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate the tissue. During asymmetric cell division, protein cell fate determinants asymmetrically localize to the opposite poles of a dividing cell to cause distinct cell fate. However, it remains unclear whether cell fate determination is robust to fluctuations and noise during this spatial allocation process. To answer this question, we engineered Caulobacter, a bacterial model for asymmetric division, to express synthetic scaffolds with modular protein interaction domains. These scaffolds perturbed the spatial distribution of the PleC-DivJ- DivK phospho-signaling network without changing their endogenous expression levels. Surprisingly, enforcing symmetrical distribution of these cell fate de terminants did not result in symmetric daughter fate or any morphological defects. Further computational analysis suggested that PleC and DivJ form a robust phospho-switch that can tolerate high amount of spatial variation. This insight may shed light on the presence of similar phospho-switches in stem cell asymmetric division regulation. Overall, our study demonstrates that synthetic protein scaffolds can provide a useful tool to probe biological systems for better understanding of their operating principles.
文摘Adaptation allows organisms to maintain a constant internal environment,which is optimised for growth.The unfolded protein response(UPR)is an example of a feedback loop that maintains endoplasmic reticulum(ER)homeostasis,and is characteristic of how adaptation is often mediated by transcriptional networks.The more recent discovery of asymmetric division in maintaining ER homeostasis,however,is an example of how alternative non-transcriptional pathways can exist,but are overlooked by gold standard transcriptomic or proteomic population-based assays.In this study,we have used a combination of fluorescent reporters,flow cytometry and mathematical modelling to explore the relative roles of asymmetric cell division and the UPR in maintaining ER homeostasis.Under low ER stress,asymmetric division leaves daughter cells with an ER deficiency,necessitating activation of the UPR and prolonged cell cycle during which they can recover ER functionality before growth.Mathematical analysis of and simulation results from our mathematical model reinforce the experimental observations that low ER stress primarily impacts the growth rate of the daughter cells.These results demonstrate the interplay between homeostatic pathways and the importance of exploring sub-population dynamics to understand population adaptation to quantitatively different stresses.
