Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis.
developmental hematopoiesis
differentiation
hematopoietic progenitors
hematopoietic stem cell
lineage tracing
scRNA-seq
self-renewal
zebrafish
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
received:
13
04
2021
revised:
29
07
2021
accepted:
20
08
2021
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
16
2
2022
Statut:
ppublish
Résumé
Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single-cell transcriptomics, we define gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a lineage-tracing approach to selectively track HSC output in situ, we find significantly delayed lymphomyeloid contribution. An inducible HSC injury model demonstrates a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage, as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding these differences could improve de novo generation and expansion of functional HSCs.
Identifiants
pubmed: 34525360
pii: S2211-1247(21)01150-5
doi: 10.1016/j.celrep.2021.109703
pmc: PMC8928453
mid: NIHMS1740537
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
109703Subventions
Organisme : NHLBI NIH HHS
ID : F31 HL152562
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007491
Pays : United States
Organisme : NICHD NIH HHS
ID : F31 HD097901
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121738
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007288
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013330
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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