The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
Manuel Viotti - One of the best experts on this subject based on the ideXlab platform.
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Sox17 links gut endoderm morphogenesis and germ layer segregation
Nature Cell Biology, 2014Co-Authors: Manuel Viotti, Sonja Nowotschin, Anna-katerina HadjantonakisAbstract:Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the Transcription Factor Sox17 in this process. Gastrulation leads to three germ layers—ectoderm, mesoderm and endoderm—that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm results from the widespread intercalation of cells of two distinct origins: pluripotent epiblast-derived definitive endoderm (DE) and extra-embryonic visceral endoderm (VE). Here we image the trajectory of prospective DE cells before intercalating into the VE epithelium. We show that the Transcription Factor Sox17, which is activated in prospective DE cells before intercalation, is necessary for gut endoderm morphogenesis and the assembly of the basement membrane that separates gut endoderm from mesoderm. Our results mechanistically link gut endoderm morphogenesis and germ layer segregation, two central and conserved features of gastrulation.
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Sox17 links gut endoderm morphogenesis and germ layer segregation
Nature Cell Biology, 2014Co-Authors: Manuel Viotti, Sonja Nowotschin, Anna-katerina HadjantonakisAbstract:Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the Transcription Factor Sox17 in this process.
Anna-katerina Hadjantonakis - One of the best experts on this subject based on the ideXlab platform.
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Sox17 links gut endoderm morphogenesis and germ layer segregation
Nature Cell Biology, 2014Co-Authors: Manuel Viotti, Sonja Nowotschin, Anna-katerina HadjantonakisAbstract:Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the Transcription Factor Sox17 in this process. Gastrulation leads to three germ layers—ectoderm, mesoderm and endoderm—that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm results from the widespread intercalation of cells of two distinct origins: pluripotent epiblast-derived definitive endoderm (DE) and extra-embryonic visceral endoderm (VE). Here we image the trajectory of prospective DE cells before intercalating into the VE epithelium. We show that the Transcription Factor Sox17, which is activated in prospective DE cells before intercalation, is necessary for gut endoderm morphogenesis and the assembly of the basement membrane that separates gut endoderm from mesoderm. Our results mechanistically link gut endoderm morphogenesis and germ layer segregation, two central and conserved features of gastrulation.
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Sox17 links gut endoderm morphogenesis and germ layer segregation
Nature Cell Biology, 2014Co-Authors: Manuel Viotti, Sonja Nowotschin, Anna-katerina HadjantonakisAbstract:Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the Transcription Factor Sox17 in this process.
Asrar B. Malik - One of the best experts on this subject based on the ideXlab platform.
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Sox17 is required for endothelial regeneration following inflammation-induced vascular injury
Nature Communications, 2019Co-Authors: Menglin Liu, Lianghui Zhang, Glenn Marsboom, Ankit Jambusaria, Shiqin Xiong, Peter T. Toth, Elizaveta V. Benevolenskaya, Jalees Rehman, Asrar B. MalikAbstract:Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental Transcription Factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate that the native endothelium itself serves as the primary source of endothelial cells repopulating the vessel wall following injury. We identify Sox17 as a key regulator of endothelial cell regeneration using endothelial-specific deletion and overexpression of Sox17. Endotoxemia upregulates Hypoxia inducible Factor 1α, which in turn Transcriptionally activates Sox17 expression. We observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. We conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis. Endothelial cell regeneration is essential for blood vessels to recover from inflammation-induced injury. Here Liu et al. show that the Transcription Factor Sox17 is required for endothelial regeneration following endotoxemia, and that delivery of a transgene expressing Sox17 to lung endothelial cells enhances recovery after injury.
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Sox17 is required for endothelial regeneration following inflammation induced vascular injury
Nature Communications, 2019Co-Authors: Menglin Liu, Lianghui Zhang, Glenn Marsboom, Ankit Jambusaria, Shiqin Xiong, Peter T. Toth, Elizaveta V. Benevolenskaya, Jalees Rehman, Asrar B. MalikAbstract:Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental Transcription Factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate that the native endothelium itself serves as the primary source of endothelial cells repopulating the vessel wall following injury. We identify Sox17 as a key regulator of endothelial cell regeneration using endothelial-specific deletion and overexpression of Sox17. Endotoxemia upregulates Hypoxia inducible Factor 1α, which in turn Transcriptionally activates Sox17 expression. We observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. We conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis.
Jeffrey A. Whitsett - One of the best experts on this subject based on the ideXlab platform.
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Sox17 is required for normal pulmonary vascular morphogenesis.
Developmental biology, 2014Co-Authors: Alexander W. Lange, Hans Michael Haitchi, Timothy D. Lecras, Anusha Sridharan, Susan E. Wert, Jeanne James, Nicholas Udell, Philipp J. Thurner, Jeffrey A. WhitsettAbstract:The SRY-box containing Transcription Factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis.
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Sox17 Promotes Cell Cycle Progression and Inhibits TGF-β/Smad3 Signaling to Initiate Progenitor Cell Behavior in the Respiratory Epithelium
PloS one, 2009Co-Authors: Alexander W. Lange, James M. Wells, Aaron M. Zorn, Angela R. Keiser, Jeffrey A. WhitsettAbstract:The Sry-related high mobility group box Transcription Factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth Factor-beta (TGF-β)-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-β1-mediated Transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and Transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.
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Sox17 influences the differentiation of respiratory epithelial cells.
Developmental biology, 2006Co-Authors: Kwon Sik Park, James M. Wells, Susan E. Wert, Aaron M. Zorn, Jeffrey A. WhitsettAbstract:Abstract The Sry-related HMG box Transcription Factor, Sox17, is required for formation of definitive endoderm that gives rise to various organs, including thyroid, lung, liver, pancreas, and intestine. While expressed at high levels in the embryonic endoderm, Sox17 is also expressed in mature tissues, including the lung. Sox17 expression in respiratory epithelial cells was first detected in the fetal lung at embryonic day 18. Thereafter, Sox17 expression was restricted primarily to ciliated cells, suggesting its potential role in airway cell differentiation. When expressed in epithelial cells of the embryonic lung, Sox17 inhibited peripheral epithelial cell differentiation and disrupted branching morphogenesis. In vitro, Sox17 inhibited Sftpc and enhanced Foxj1 promoter activity, consistent with its expression in proximal airway cells. Conditional expression of Sox17 in peripheral respiratory epithelial cells of adult lung induced hyperplastic clusters of cells expressing increased levels of β-catenin and differentiation markers representing multiple proximal respiratory epithelial cell types. Sox17 prolonged survival and enhanced growth and differentiation of respiratory epithelial cells in vitro. Sox17 induced plasticity of respiratory epithelial cells, reprogramming alveolar cells into epithelial cells with characteristics more typical of the proximal airway. Sites of expression and the effects of Sox17 in vivo and in vitro are consistent with a role for Sox17 or other members of the Sox family of Transcription Factors in differentiation of the conducting airway epithelium.
Sonja Nowotschin - One of the best experts on this subject based on the ideXlab platform.
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Sox17 links gut endoderm morphogenesis and germ layer segregation
Nature Cell Biology, 2014Co-Authors: Manuel Viotti, Sonja Nowotschin, Anna-katerina HadjantonakisAbstract:Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the Transcription Factor Sox17 in this process. Gastrulation leads to three germ layers—ectoderm, mesoderm and endoderm—that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm results from the widespread intercalation of cells of two distinct origins: pluripotent epiblast-derived definitive endoderm (DE) and extra-embryonic visceral endoderm (VE). Here we image the trajectory of prospective DE cells before intercalating into the VE epithelium. We show that the Transcription Factor Sox17, which is activated in prospective DE cells before intercalation, is necessary for gut endoderm morphogenesis and the assembly of the basement membrane that separates gut endoderm from mesoderm. Our results mechanistically link gut endoderm morphogenesis and germ layer segregation, two central and conserved features of gastrulation.
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Sox17 links gut endoderm morphogenesis and germ layer segregation
Nature Cell Biology, 2014Co-Authors: Manuel Viotti, Sonja Nowotschin, Anna-katerina HadjantonakisAbstract:Using time-lapse imaging Hadjantonakis and colleagues have characterized the intercalation of definitive endoderm progenitors into the overlying visceral endoderm during mouse gastrulation and demonstrated a role for the Transcription Factor Sox17 in this process.