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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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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. |
format | Online Article Text |
id | pubmed-8478150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
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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