The Nuclear Receptor Corepressor NCoR1 Regulates Hematopoiesis and Leukemogenesis in Vivo

Overview

Journal Blood Adv

Specialty Hematology

Date 2019 Feb 27

PMID 30804018

Citations 8

Authors

Xiaoling Wan

Lulu Liu

Peipei Zhou

Xinhui Hui

Qiaomei He

Fangfang Yu

Wei Zhang

Xiaodan Ding

Xiujie Yuan

Na Zhang

Yingxi Zhao

Ruihong Zhu

YuanHua Liu

Pei Hao

Johan Auwerx

Xianmin Song

Qibin Leng

Yan Zhang

Affiliations

Soon will be listed here.

Abstract

Enhanced understanding of normal and malignant hematopoiesis pathways should facilitate the development of effective clinical treatment strategies for hematopoietic malignancies. Nuclear receptor corepressor 1 (NCoR1) has been implicated in transcriptional repression and embryonic organ development, but its role in hematopoiesis is yet to be fully elucidated. Here, we showed that hematopoietic-specific loss of leads to expansion of the hematopoietic stem cell (HSC) pool due to aberrant cell cycle entry of long-term HSCs under steady-state conditions. Moreover, -deficient HSCs exhibited normal self-renewal capacity but severely impaired lymphoid-differentiation potential in competitive hematopoietic-reconstitution assays. Transcriptome analysis further revealed that several hematopoiesis-associated genes are regulated by NCoR1. In addition, deficiency in hematopoietic cells delayed the course of leukemia and promoted leukemia cell differentiation in an MLL-AF9-induced mouse model. NCoR1 and its partner, histone deacetylase 3, can modulate histone acetylation and gene transcription through binding the promoter regions of myeloid-differentiation genes. Our collective results support the critical involvement of NCoR1 in normal and malignant hematopoiesis in vivo.

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