Wan, XiaolingLiu, LuluZhou, PeipeiHui, XinhuiHe, QiaomeiYu, FangfangZhang, WeiDing, XiaodanYuan, XiujieZhang, NaZhao, YingxiZhu, RuihongLiu, YuanhuaHao, PeiAuwerx, JohanSong, XianminLeng, QibinZhang, Yan2019-06-182019-06-182019-06-182019-02-2610.1182/bloodadvances.2018022756https://infoscience.epfl.ch/handle/20.500.14299/157984WOS:000459729800018Enhanced 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 NCoR1 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, NCoR1-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, NCoR1 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.Hematologyacute myeloid-leukemiastem-cellco-repressorn-corerythroid-differentiationself-renewalhdac3smrttranscriptionproteintext::journal::journal article::research article