Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
01 Jan 2024
01 Jan 2024
Historique:
received:
16
06
2023
revised:
18
09
2023
accepted:
13
10
2023
pmc-release:
01
05
2024
medline:
2
11
2023
pubmed:
1
11
2023
entrez:
1
11
2023
Statut:
ppublish
Résumé
The dynamics of the hematopoietic flux responsible for blood cell production in native conditions remains a matter of debate. Using CITE-seq analyses, we uncovered a distinct progenitor population that displays a cell cycle gene signature similar to the one found in quiescent hematopoietic stem cells. We further determined that the CD62L marker can be used to phenotypically enrich this population in the Flt3+ multipotent progenitor (MPP4) compartment. Functional in vitro and in vivo analyses validated the heterogeneity of the MPP4 compartment and established the quiescent/slow-cycling properties of the CD62L- MPP4 cells. Furthermore, studies under native conditions revealed a novel hierarchical organization of the MPP compartments in which quiescent/slow-cycling MPP4 cells sustain a prolonged hematopoietic activity at steady-state while giving rise to other lineage-biased MPP populations. Altogether, our data characterize a durable and productive quiescent/slow-cycling hematopoietic intermediary within the MPP4 compartment and highlight early paths of progenitor differentiation during unperturbed hematopoiesis.
Identifiants
pubmed: 37910046
pii: 276374
doi: 10.1084/jem.20231035
pmc: PMC10620607
pii:
doi:
Substances chimiques
FLT3 protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL122661
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121062
Pays : United States
Organisme : NIH HHS
ID : S10 OD025045
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151654
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK133145
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK126108
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141418
Pays : United States
Organisme : NIH HHS
ID : R01HL141418
Pays : United States
Informations de copyright
© 2023 Solomon et al.
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