Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.


Dahai Wang, Mayuri Tanaka-Yano, Eleanor Meader, Melissa A Kinney, Vivian Morris, Edroaldo Lummertz da Rocha, Nan Liu, Tianxin Liu, Qian Zhu, Stuart H Orkin, Trista E North, George Q Daley, R Grant Rowe. Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis. Cell reports. 2022 Apr 05;39(1):110587

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 35385744

View Full Text