Regulates Quiescence and Differentiation of Adult Hematopoietic Stem Cells by Restricting RNA Polymerase II Elongation

Overview

Journal Haematologica

Specialty Hematology

Date 2018 Apr 14

PMID 29650642

Citations 20

Authors

Yile Zhou

Xiaomei Yan

Xiaomin Feng

Jiachen Bu

Yunzhu Dong

Peipei Lin

Yoshihiro Hayashi

Rui Huang

Andre Olsson

Paul R Andreassen

H Leighton Grimes

Qian-Fei Wang

Tao Cheng

Zhijian Xiao

Jie Jin

Gang Huang

Affiliations

Soon will be listed here.

Abstract

(), encoding a histone methyltransferase, is associated with many hematopoietic diseases when mutated. By generating a novel exon 6 conditional knockout mouse model, we describe an essential role of in maintaining the adult hematopoietic stem cells. Loss of results in leukopenia, anemia, and increased platelets accompanied by hypocellularity, erythroid dysplasia, and mild fibrosis in bone marrow. knockout mice show significantly decreased hematopoietic stem and progenitor cells except for erythroid progenitors. knockout hematopoietic stem cells fail to establish long-term bone marrow reconstitution after transplantation because of the loss of quiescence, increased apoptosis, and reduced multiple-lineage terminal differentiation potential. Bioinformatic analysis revealed that the hematopoietic stem cells exit from quiescence and commit to differentiation, which lead to hematopoietic stem cell exhaustion. Mechanistically, we attribute an important function in murine adult hematopoietic stem cells to the inhibition of the Nsd1/2/3 transcriptional complex, which recruits super elongation complex and controls RNA polymerase II elongation on a subset of target genes, including Our results reveal a critical role of in regulating quiescence and differentiation of hematopoietic stem cells through restricting the NSDs/SEC mediated RNA polymerase II elongation.

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