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Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells

The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes...

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Autores principales: Gattiglio, Marina, Protzek, Michelle, Schröter, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445724/
https://www.ncbi.nlm.nih.gov/pubmed/37530863
http://dx.doi.org/10.1242/bio.059941
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author Gattiglio, Marina
Protzek, Michelle
Schröter, Christian
author_facet Gattiglio, Marina
Protzek, Michelle
Schröter, Christian
author_sort Gattiglio, Marina
collection PubMed
description The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes in mammals have been mapped in detail, but how FGF shapes mesodermal cell type diversity is not precisely known. It is also not clear how FGF signaling integrates with the activity of other signaling systems involved in mesoderm differentiation. Here, we address these questions by analyzing the effects of targeted signaling manipulations in differentiating stem cell populations at single-cell resolution. We identify opposing functions of BMP and FGF, and map FGF-dependent and -independent mesodermal lineages. Stimulation with exogenous FGF boosts the expression of endogenous Fgf genes while repressing Bmp ligand genes. This positive autoregulation of FGF signaling, coupled with the repression of BMP signaling, may contribute to the specification of reproducible and coherent cohorts of cells with the same identity via a community effect, both in the embryo and in synthetic embryo-like systems.
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spelling pubmed-104457242023-08-24 Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells Gattiglio, Marina Protzek, Michelle Schröter, Christian Biol Open Research Article The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes in mammals have been mapped in detail, but how FGF shapes mesodermal cell type diversity is not precisely known. It is also not clear how FGF signaling integrates with the activity of other signaling systems involved in mesoderm differentiation. Here, we address these questions by analyzing the effects of targeted signaling manipulations in differentiating stem cell populations at single-cell resolution. We identify opposing functions of BMP and FGF, and map FGF-dependent and -independent mesodermal lineages. Stimulation with exogenous FGF boosts the expression of endogenous Fgf genes while repressing Bmp ligand genes. This positive autoregulation of FGF signaling, coupled with the repression of BMP signaling, may contribute to the specification of reproducible and coherent cohorts of cells with the same identity via a community effect, both in the embryo and in synthetic embryo-like systems. The Company of Biologists Ltd 2023-08-17 /pmc/articles/PMC10445724/ /pubmed/37530863 http://dx.doi.org/10.1242/bio.059941 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Gattiglio, Marina
Protzek, Michelle
Schröter, Christian
Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
title Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
title_full Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
title_fullStr Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
title_full_unstemmed Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
title_short Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells
title_sort population-level antagonism between fgf and bmp signaling steers mesoderm differentiation in embryonic stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445724/
https://www.ncbi.nlm.nih.gov/pubmed/37530863
http://dx.doi.org/10.1242/bio.059941
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