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Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo

During embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSCs). Although previous studies have shown that yolk-sac-derived erythromyeloid progenitors and HSCs emerge from distinct populations of...

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Autores principales: Dignum, Tessa, Varnum-Finney, Barbara, Srivatsan, Sanjay R., Dozono, Stacey, Waltner, Olivia, Heck, Adam M., Ishida, Takashi, Nourigat-McKay, Cynthia, Jackson, Dana L., Rafii, Shahin, Trapnell, Cole, Bernstein, Irwin D., Hadland, Brandon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478150/
https://www.ncbi.nlm.nih.gov/pubmed/34525376
http://dx.doi.org/10.1016/j.celrep.2021.109675
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author Dignum, Tessa
Varnum-Finney, Barbara
Srivatsan, Sanjay R.
Dozono, Stacey
Waltner, Olivia
Heck, Adam M.
Ishida, Takashi
Nourigat-McKay, Cynthia
Jackson, Dana L.
Rafii, Shahin
Trapnell, Cole
Bernstein, Irwin D.
Hadland, Brandon
author_facet Dignum, Tessa
Varnum-Finney, Barbara
Srivatsan, Sanjay R.
Dozono, Stacey
Waltner, Olivia
Heck, Adam M.
Ishida, Takashi
Nourigat-McKay, Cynthia
Jackson, Dana L.
Rafii, Shahin
Trapnell, Cole
Bernstein, Irwin D.
Hadland, Brandon
author_sort Dignum, Tessa
collection PubMed
description During embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSCs). Although previous studies have shown that yolk-sac-derived erythromyeloid progenitors and HSCs emerge from distinct populations of HE, it remains unknown whether the earliest lymphoid-competent progenitors, multipotent progenitors, and HSCs originate from common HE. In this study, we demonstrate by clonal assays and single-cell transcriptomics that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSCs. Specifically, HSC-competent HE are characterized by expression of CXCR4 surface marker and by higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal. Taken together, these findings suggest a revised model of developmental hematopoiesis in which the initial populations of multipotent progenitors and HSCs arise independently from HE with distinct phenotypic and transcriptional properties.
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spelling pubmed-84781502021-09-28 Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo Dignum, Tessa Varnum-Finney, Barbara Srivatsan, Sanjay R. Dozono, Stacey Waltner, Olivia Heck, Adam M. Ishida, Takashi Nourigat-McKay, Cynthia Jackson, Dana L. Rafii, Shahin Trapnell, Cole Bernstein, Irwin D. Hadland, Brandon Cell Rep Article During embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSCs). Although previous studies have shown that yolk-sac-derived erythromyeloid progenitors and HSCs emerge from distinct populations of HE, it remains unknown whether the earliest lymphoid-competent progenitors, multipotent progenitors, and HSCs originate from common HE. In this study, we demonstrate by clonal assays and single-cell transcriptomics that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSCs. Specifically, HSC-competent HE are characterized by expression of CXCR4 surface marker and by higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal. Taken together, these findings suggest a revised model of developmental hematopoiesis in which the initial populations of multipotent progenitors and HSCs arise independently from HE with distinct phenotypic and transcriptional properties. 2021-09-14 /pmc/articles/PMC8478150/ /pubmed/34525376 http://dx.doi.org/10.1016/j.celrep.2021.109675 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Dignum, Tessa
Varnum-Finney, Barbara
Srivatsan, Sanjay R.
Dozono, Stacey
Waltner, Olivia
Heck, Adam M.
Ishida, Takashi
Nourigat-McKay, Cynthia
Jackson, Dana L.
Rafii, Shahin
Trapnell, Cole
Bernstein, Irwin D.
Hadland, Brandon
Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
title Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
title_full Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
title_fullStr Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
title_full_unstemmed Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
title_short Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
title_sort multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478150/
https://www.ncbi.nlm.nih.gov/pubmed/34525376
http://dx.doi.org/10.1016/j.celrep.2021.109675
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