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Metabolic control of cell fate bifurcations in a hematopoietic progenitor population
Author(s) -
Kratchmarov Radomir,
Viragova Sara,
Kim Min Jung,
Rothman Nyanza J,
Liu Kang,
Reizis Boris,
Reiner Steven L
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12040
Subject(s) - biology , microbiology and biotechnology , progenitor cell , haematopoiesis , population , cellular differentiation , stem cell , genetics , demography , sociology , gene
Growth signals drive hematopoietic progenitor cells to proliferate and branch into divergent cell fates, but how unequal outcomes arise from a common progenitor is not fully understood. We used steady‐state analysis of in vivo hematopoiesis and Fms‐related tyrosine kinase 3 ligand (Flt3L)‐induced in vitro differentiation of dendritic cells (DCs) to determine how growth signals regulate lineage bias. We found that Flt3L signaling induced anabolic activation and proliferation of DC progenitors, which was associated with DC differentiation. Perturbation of processes associated with quiescence and catabolism, including AMP‐activated protein kinase signaling, fatty acid oxidation, or mitochondrial clearance increased development of cDC2 cells at the expense of cDC1 cells. Conversely, scavenging anabolism‐associated reactive oxygen species skewed differentiation toward cDC1 cells. Sibling daughter cells of dividing DC progenitors exhibited unequal expression of the transcription factor interferon regulatory factor 8, which correlated with clonal divergence in FoxO3a signaling and population‐level bifurcation of cell fate. We propose that unequal transmission of growth signals during cell division might support fate branches during proliferative expansion of progenitors.