RRC ID 74615
Author Wang D, Tanaka-Yano M, Meader E, Kinney MA, Morris V, Lummertz da Rocha E, Liu N, Liu T, Zhu Q, Orkin SH, North TE, Daley GQ, Rowe RG.
Title Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis.
Journal Cell Rep
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 bias, and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a mechanism of regulation of HSPC output via chromatin modification as a function of age with potential impact on age-biased pediatric and adult blood disorders.
Volume 39(1)
Pages 110587
Published 2022-4-5
DOI 10.1016/j.celrep.2022.110587
PII S2211-1247(22)00331-X
PMID 35385744
PMC PMC9029260
MeSH Adult Animals Child Gene Regulatory Networks Hematopoiesis* / genetics Hematopoietic Stem Cells* / metabolism Humans Infant, Newborn Lymphopoiesis Mice MicroRNAs* Polycomb Repressive Complex 1* / genetics Polycomb Repressive Complex 1* / metabolism Polycomb-Group Proteins / metabolism RNA-Binding Proteins* / genetics RNA-Binding Proteins* / metabolism
IF 8.109
Human and Animal Cells HUDEP-1(RCB4556) HUDEP-2(RCB4557)