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.
Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions
Disclosures: J.A. Cancelas reported “other” from Preservation Bio and Platefuse and grants from Cerus Co., TerumoBCT, Velico, Teleflex, and Westat outside the submitted work. No other disclosures were reported.
- Award Id(s): R01HL141418,R01DK133145,R01HL122661,R01DK121062,S10OD025045
- Award Id(s): U54 DK126108
Michael Solomon, Baobao Song, Vinothini Govindarajah, Samantha Good, Ashok Arasu, E. Broderick Hinton, Kairavee Thakkar, James Bartram, Marie-Dominique Filippi, Jose A. Cancelas, Nathan Salomonis, H. Leighton Grimes, Damien Reynaud; Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions. J Exp Med 1 January 2024; 221 (1): e20231035. doi: https://doi.org/10.1084/jem.20231035
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