Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis.

ABSTRACT: Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7's control of hematopoietic maturation. We find that juvenile Cbx2^-/- hematopoietic tissues show impairment of B-lymphopoiesis, a precocious adult-like myeloid

SUBMITTER: Wang D 

PROVIDER: S-EPMC9029260 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature