Pub Date : 2023-11-27Epub Date: 2023-07-24DOI: 10.1146/annurev-genet-031423-120918
Claudius F Kratochwil, Ricardo Mallarino
Vertebrates exhibit a wide range of color patterns, which play critical roles in mediating intra- and interspecific communication. Because of their diversity and visual accessibility, color patterns offer a unique and fascinating window into the processes underlying biological organization. In this review, we focus on describing many of the general principles governing the formation and evolution of color patterns in different vertebrate groups. We characterize the types of patterns, review the molecular and developmental mechanisms by which they originate, and discuss their role in constraining or facilitating evolutionary change. Lastly, we outline outstanding questions in the field and discuss different approaches that can be used to address them. Overall, we provide a unifying conceptual framework among vertebrate systems that may guide research into naturally evolved mechanisms underlying color pattern formation and evolution.
{"title":"Mechanisms Underlying the Formation and Evolution of Vertebrate Color Patterns.","authors":"Claudius F Kratochwil, Ricardo Mallarino","doi":"10.1146/annurev-genet-031423-120918","DOIUrl":"10.1146/annurev-genet-031423-120918","url":null,"abstract":"<p><p>Vertebrates exhibit a wide range of color patterns, which play critical roles in mediating intra- and interspecific communication. Because of their diversity and visual accessibility, color patterns offer a unique and fascinating window into the processes underlying biological organization. In this review, we focus on describing many of the general principles governing the formation and evolution of color patterns in different vertebrate groups. We characterize the types of patterns, review the molecular and developmental mechanisms by which they originate, and discuss their role in constraining or facilitating evolutionary change. Lastly, we outline outstanding questions in the field and discuss different approaches that can be used to address them. Overall, we provide a unifying conceptual framework among vertebrate systems that may guide research into naturally evolved mechanisms underlying color pattern formation and evolution.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"135-156"},"PeriodicalIF":8.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9864966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-06-29DOI: 10.1146/annurev-genet-022223-093643
Haley A Vecchiarelli, Marie-Ève Tremblay
Microglia, the resident immune cells of the central nervous system (CNS), are primarily derived from the embryonic yolk sac and make their way to the CNS during early development. They play key physiological and immunological roles across the life span, throughout health, injury, and disease. Recent transcriptomic studies have identified gene transcript signatures expressed by microglia that may provide the foundation for unprecedented insights into their functions. Microglial gene expression signatures can help distinguish them from macrophage cell types to a reasonable degree of certainty, depending on the context. Microglial expression patterns further suggest a heterogeneous population comprised of many states that vary according to the spatiotemporal context. Microglial diversity is most pronounced during development, when extensive CNS remodeling takes place, and following disease or injury. A next step of importance for the field will be to identify the functional roles performed by these various microglial states, with the perspective of targeting them therapeutically.
{"title":"Microglial Transcriptional Signatures in the Central Nervous System: Toward A Future of Unraveling Their Function in Health and Disease.","authors":"Haley A Vecchiarelli, Marie-Ève Tremblay","doi":"10.1146/annurev-genet-022223-093643","DOIUrl":"10.1146/annurev-genet-022223-093643","url":null,"abstract":"<p><p>Microglia, the resident immune cells of the central nervous system (CNS), are primarily derived from the embryonic yolk sac and make their way to the CNS during early development. They play key physiological and immunological roles across the life span, throughout health, injury, and disease. Recent transcriptomic studies have identified gene transcript signatures expressed by microglia that may provide the foundation for unprecedented insights into their functions. Microglial gene expression signatures can help distinguish them from macrophage cell types to a reasonable degree of certainty, depending on the context. Microglial expression patterns further suggest a heterogeneous population comprised of many states that vary according to the spatiotemporal context. Microglial diversity is most pronounced during development, when extensive CNS remodeling takes place, and following disease or injury. A next step of importance for the field will be to identify the functional roles performed by these various microglial states, with the perspective of targeting them therapeutically.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"65-86"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-09-18DOI: 10.1146/annurev-genet-033123-095833
Madhura Kulkarni, J Marie Hardwick
Programmed cell death (self-induced) is intrinsic to all cellular life forms, including unicellular organisms. However, cell death research has focused on animal models to understand cancer, degenerative disorders, and developmental processes. Recently delineated suicidal death mechanisms in bacteria and fungi have revealed ancient origins of animal cell death that are intertwined with immune mechanisms, allaying earlier doubts that self-inflicted cell death pathways exist in microorganisms. Approximately 20 mammalian death pathways have been partially characterized over the last 35 years. By contrast, more than 100 death mechanisms have been identified in bacteria and a few fungi in recent years. However, cell death is nearly unstudied in most human pathogenic microbes that cause major public health burdens. Here, we consider how the current understanding of programmed cell death arose through animal studies and how recently uncovered microbial cell death mechanisms in fungi and bacteria resemble and differ from mechanisms of mammalian cell death.
{"title":"Programmed Cell Death in Unicellular Versus Multicellular Organisms.","authors":"Madhura Kulkarni, J Marie Hardwick","doi":"10.1146/annurev-genet-033123-095833","DOIUrl":"10.1146/annurev-genet-033123-095833","url":null,"abstract":"<p><p>Programmed cell death (self-induced) is intrinsic to all cellular life forms, including unicellular organisms. However, cell death research has focused on animal models to understand cancer, degenerative disorders, and developmental processes. Recently delineated suicidal death mechanisms in bacteria and fungi have revealed ancient origins of animal cell death that are intertwined with immune mechanisms, allaying earlier doubts that self-inflicted cell death pathways exist in microorganisms. Approximately 20 mammalian death pathways have been partially characterized over the last 35 years. By contrast, more than 100 death mechanisms have been identified in bacteria and a few fungi in recent years. However, cell death is nearly unstudied in most human pathogenic microbes that cause major public health burdens. Here, we consider how the current understanding of programmed cell death arose through animal studies and how recently uncovered microbial cell death mechanisms in fungi and bacteria resemble and differ from mechanisms of mammalian cell death.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"435-459"},"PeriodicalIF":8.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-08-10DOI: 10.1146/annurev-genet-022123-110824
Mark A A Minow, Alexandre P Marand, Robert J Schmitz
The ease and throughput of single-cell genomics have steadily improved, and its current trajectory suggests that surveying single-cell populations will become routine. We discuss the merger of quantitative genetics with single-cell genomics and emphasize how this synergizes with advantages intrinsic to plants. Single-cell population genomics provides increased detection resolution when mapping variants that control molecular traits, including gene expression or chromatin accessibility. Additionally, single-cell population genomics reveals the cell types in which variants act and, when combined with organism-level phenotype measurements, unveils which cellular contexts impact higher-order traits. Emerging technologies, notably multiomics, can facilitate the measurement of both genetic changes and genomic traits in single cells, enabling single-cell genetic experiments. The implementation of single-cell genetics will advance the investigation of the genetic architecture of complex molecular traits and provide new experimental paradigms to study eukaryotic genetics.
{"title":"Leveraging Single-Cell Populations to Uncover the Genetic Basis of Complex Traits.","authors":"Mark A A Minow, Alexandre P Marand, Robert J Schmitz","doi":"10.1146/annurev-genet-022123-110824","DOIUrl":"10.1146/annurev-genet-022123-110824","url":null,"abstract":"<p><p>The ease and throughput of single-cell genomics have steadily improved, and its current trajectory suggests that surveying single-cell populations will become routine. We discuss the merger of quantitative genetics with single-cell genomics and emphasize how this synergizes with advantages intrinsic to plants. Single-cell population genomics provides increased detection resolution when mapping variants that control molecular traits, including gene expression or chromatin accessibility. Additionally, single-cell population genomics reveals the cell types in which variants act and, when combined with organism-level phenotype measurements, unveils which cellular contexts impact higher-order traits. Emerging technologies, notably multiomics, can facilitate the measurement of both genetic changes and genomic traits in single cells, enabling single-cell genetic experiments. The implementation of single-cell genetics will advance the investigation of the genetic architecture of complex molecular traits and provide new experimental paradigms to study eukaryotic genetics.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"297-319"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-08-16DOI: 10.1146/annurev-genet-071719-020641
Laurent Formery, Christopher J Lowe
The goal of comparative developmental biology is identifying mechanistic differences in embryonic development between different taxa and how these evolutionary changes have led to morphological and organizational differences in adult body plans. Much of this work has focused on direct-developing species in which the adult forms straight from the embryo and embryonic modifications have direct effects on the adult. However, most animal lineages are defined by indirect development, in which the embryo gives rise to a larval body plan and the adult forms by transformation of the larva. Historically, much of our understanding of complex life cycles is viewed through the lenses of ecology and zoology. In this review, we discuss the importance of establishing developmental rather than morphological or ecological criteria for defining developmental mode and explicitly considering the evolutionary implications of incorporating complex life cycles into broad developmental comparisons of embryos across metazoans.
{"title":"Integrating Complex Life Cycles in Comparative Developmental Biology.","authors":"Laurent Formery, Christopher J Lowe","doi":"10.1146/annurev-genet-071719-020641","DOIUrl":"10.1146/annurev-genet-071719-020641","url":null,"abstract":"<p><p>The goal of comparative developmental biology is identifying mechanistic differences in embryonic development between different taxa and how these evolutionary changes have led to morphological and organizational differences in adult body plans. Much of this work has focused on direct-developing species in which the adult forms straight from the embryo and embryonic modifications have direct effects on the adult. However, most animal lineages are defined by indirect development, in which the embryo gives rise to a larval body plan and the adult forms by transformation of the larva. Historically, much of our understanding of complex life cycles is viewed through the lenses of ecology and zoology. In this review, we discuss the importance of establishing developmental rather than morphological or ecological criteria for defining developmental mode and explicitly considering the evolutionary implications of incorporating complex life cycles into broad developmental comparisons of embryos across metazoans.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"321-339"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-09-18DOI: 10.1146/annurev-genet-071719-021856
Stewart Shuman
Enzymes that phosphorylate, dephosphorylate, and ligate RNA 5' and 3' ends were discovered more than half a century ago and were eventually shown to repair purposeful site-specific endonucleolytic breaks in the RNA phosphodiester backbone. The pace of discovery and characterization of new candidate RNA repair activities in taxa from all phylogenetic domains greatly exceeds our understanding of the biological pathways in which they act. The key questions anent RNA break repair in vivo are (a) identifying the triggers, agents, and targets of RNA cleavage and (b) determining whether RNA repair results in restoration of the original RNA, modification of the RNA (by loss or gain at the ends), or rearrangements of the broken RNA segments (i.e., RNA recombination). This review provides a perspective on the discovery, mechanisms, and physiology of purposeful RNA break repair, highlighting exemplary repair pathways (e.g., tRNA restriction-repair and tRNA splicing) for which genetics has figured prominently in their elucidation.
{"title":"RNA Repair: Hiding in Plain Sight.","authors":"Stewart Shuman","doi":"10.1146/annurev-genet-071719-021856","DOIUrl":"10.1146/annurev-genet-071719-021856","url":null,"abstract":"<p><p>Enzymes that phosphorylate, dephosphorylate, and ligate RNA 5' and 3' ends were discovered more than half a century ago and were eventually shown to repair purposeful site-specific endonucleolytic breaks in the RNA phosphodiester backbone. The pace of discovery and characterization of new candidate RNA repair activities in taxa from all phylogenetic domains greatly exceeds our understanding of the biological pathways in which they act. The key questions anent RNA break repair in vivo are (<i>a</i>) identifying the triggers, agents, and targets of RNA cleavage and (<i>b</i>) determining whether RNA repair results in restoration of the original RNA, modification of the RNA (by loss or gain at the ends), or rearrangements of the broken RNA segments (i.e., RNA recombination). This review provides a perspective on the discovery, mechanisms, and physiology of purposeful RNA break repair, highlighting exemplary repair pathways (e.g., tRNA restriction-repair and tRNA splicing) for which genetics has figured prominently in their elucidation.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"461-489"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-08-10DOI: 10.1146/annurev-genet-072920-013842
Daniel Schraivogel, Lars M Steinmetz, Leopold Parts
Assigning functions to genes and learning how to control their expression are part of the foundation of cell biology and therapeutic development. An efficient and unbiased method to accomplish this is genetic screening, which historically required laborious clone generation and phenotyping and is still limited by scale today. The rapid technological progress on modulating gene function with CRISPR-Cas and measuring it in individual cells has now relaxed the major experimental constraints and enabled pooled screening with complex readouts from single cells. Here, we review the principles and practical considerations for pooled single-cell CRISPR screening. We discuss perturbation strategies, experimental model systems, matching the perturbation to the individual cells, reading out cell phenotypes, and data analysis. Our focus is on single-cell RNA sequencing and cell sorting-based readouts, including image-enabled cell sorting. We expect this transformative approach to fuel biomedical research for the next several decades.
{"title":"Pooled Genome-Scale CRISPR Screens in Single Cells.","authors":"Daniel Schraivogel, Lars M Steinmetz, Leopold Parts","doi":"10.1146/annurev-genet-072920-013842","DOIUrl":"10.1146/annurev-genet-072920-013842","url":null,"abstract":"<p><p>Assigning functions to genes and learning how to control their expression are part of the foundation of cell biology and therapeutic development. An efficient and unbiased method to accomplish this is genetic screening, which historically required laborious clone generation and phenotyping and is still limited by scale today. The rapid technological progress on modulating gene function with CRISPR-Cas and measuring it in individual cells has now relaxed the major experimental constraints and enabled pooled screening with complex readouts from single cells. Here, we review the principles and practical considerations for pooled single-cell CRISPR screening. We discuss perturbation strategies, experimental model systems, matching the perturbation to the individual cells, reading out cell phenotypes, and data analysis. Our focus is on single-cell RNA sequencing and cell sorting-based readouts, including image-enabled cell sorting. We expect this transformative approach to fuel biomedical research for the next several decades.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"223-244"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-09-18DOI: 10.1146/annurev-genet-072320-125436
Marie R Jacobovitz, Elizabeth A Hambleton, Annika Guse
Symbiotic interactions occur in all domains of life, providing organisms with resources to adapt to new habitats. A prime example is the endosymbiosis between corals and photosynthetic dinoflagellates. Eukaryotic dinoflagellate symbionts reside inside coral cells and transfer essential nutrients to their hosts, driving the productivity of the most biodiverse marine ecosystem. Recent advances in molecular and genomic characterization have revealed symbiosis-specific genes and mechanisms shared among symbiotic cnidarians. In this review, we focus on the cellular and molecular processes that underpin the interaction between symbiont and host. We discuss symbiont acquisition via phagocytosis, modulation of host innate immunity, symbiont integration into host cell metabolism, and nutrient exchange as a fundamental aspect of stable symbiotic associations. We emphasize the importance of using model systems to dissect the cellular complexity of endosymbiosis, which ultimately serves as the basis for understanding its ecology and capacity to adapt in the face of climate change.
{"title":"Unlocking the Complex Cell Biology of Coral-Dinoflagellate Symbiosis: A Model Systems Approach.","authors":"Marie R Jacobovitz, Elizabeth A Hambleton, Annika Guse","doi":"10.1146/annurev-genet-072320-125436","DOIUrl":"10.1146/annurev-genet-072320-125436","url":null,"abstract":"<p><p>Symbiotic interactions occur in all domains of life, providing organisms with resources to adapt to new habitats. A prime example is the endosymbiosis between corals and photosynthetic dinoflagellates. Eukaryotic dinoflagellate symbionts reside inside coral cells and transfer essential nutrients to their hosts, driving the productivity of the most biodiverse marine ecosystem. Recent advances in molecular and genomic characterization have revealed symbiosis-specific genes and mechanisms shared among symbiotic cnidarians. In this review, we focus on the cellular and molecular processes that underpin the interaction between symbiont and host. We discuss symbiont acquisition via phagocytosis, modulation of host innate immunity, symbiont integration into host cell metabolism, and nutrient exchange as a fundamental aspect of stable symbiotic associations. We emphasize the importance of using model systems to dissect the cellular complexity of endosymbiosis, which ultimately serves as the basis for understanding its ecology and capacity to adapt in the face of climate change.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"411-434"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-09-14DOI: 10.1146/annurev-genet-022123-113904
María Mercedes Zambrano
Antibiotic resistance genes predate the therapeutic uses of antibiotics. However, the current antimicrobial resistance crisis stems from our extensive use of antibiotics and the generation of environmental stressors that impose new selective pressure on microbes and drive the evolution of resistant pathogens that now threaten human health. Similar to climate change, this global threat results from human activities that change habitats and natural microbiomes, which in turn interact with human-associated ecosystems and lead to adverse impacts on human health. Human activities that alter our planet at global scales exacerbate the current resistance crisis and exemplify our central role in large-scale changes in which we are both protagonists and architects of our success but also casualties of unanticipated collateral outcomes. As cognizant participants in this ongoing planetary experiment, we are driven to understand and find strategies to curb the ongoing crises of resistance and climate change.
{"title":"Interplay Between Antimicrobial Resistance and Global Environmental Change.","authors":"María Mercedes Zambrano","doi":"10.1146/annurev-genet-022123-113904","DOIUrl":"10.1146/annurev-genet-022123-113904","url":null,"abstract":"<p><p>Antibiotic resistance genes predate the therapeutic uses of antibiotics. However, the current antimicrobial resistance crisis stems from our extensive use of antibiotics and the generation of environmental stressors that impose new selective pressure on microbes and drive the evolution of resistant pathogens that now threaten human health. Similar to climate change, this global threat results from human activities that change habitats and natural microbiomes, which in turn interact with human-associated ecosystems and lead to adverse impacts on human health. Human activities that alter our planet at global scales exacerbate the current resistance crisis and exemplify our central role in large-scale changes in which we are both protagonists and architects of our success but also casualties of unanticipated collateral outcomes. As cognizant participants in this ongoing planetary experiment, we are driven to understand and find strategies to curb the ongoing crises of resistance and climate change.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"275-296"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27Epub Date: 2023-09-14DOI: 10.1146/annurev-genet-022123-090319
Ayodeji Adegunsoye, Natalia M Gonzales, Yoav Gilad
Many human phenotypes are impossible to recapitulate in model organisms or immortalized human cell lines. Induced pluripotent stem cells (iPSCs) offer a way to study disease mechanisms in a variety of differentiated cell types while circumventing ethical and practical issues associated with finite tissue sources and postmortem states. Here, we discuss the broad utility of iPSCs in genetic medicine and describe how they are being used to study musculoskeletal, pulmonary, neurologic, and cardiac phenotypes. We summarize the particular challenges presented by each organ system and describe how iPSC models are being used to address them. Finally, we discuss emerging iPSC-derived organoid models and the potential value that they can bring to studies of human disease.
{"title":"Induced Pluripotent Stem Cells in Disease Biology and the Evidence for Their In Vitro Utility.","authors":"Ayodeji Adegunsoye, Natalia M Gonzales, Yoav Gilad","doi":"10.1146/annurev-genet-022123-090319","DOIUrl":"10.1146/annurev-genet-022123-090319","url":null,"abstract":"<p><p>Many human phenotypes are impossible to recapitulate in model organisms or immortalized human cell lines. Induced pluripotent stem cells (iPSCs) offer a way to study disease mechanisms in a variety of differentiated cell types while circumventing ethical and practical issues associated with finite tissue sources and postmortem states. Here, we discuss the broad utility of iPSCs in genetic medicine and describe how they are being used to study musculoskeletal, pulmonary, neurologic, and cardiac phenotypes. We summarize the particular challenges presented by each organ system and describe how iPSC models are being used to address them. Finally, we discuss emerging iPSC-derived organoid models and the potential value that they can bring to studies of human disease.</p>","PeriodicalId":8035,"journal":{"name":"Annual review of genetics","volume":" ","pages":"341-360"},"PeriodicalIF":11.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10240258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}