2. Academic Validation
  3. HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells

HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells

  • EMBO Rep. 2023 Aug 29;e56009. doi: 10.15252/embr.202256009.
Jia Yang # 1,  Yang Liu # 1,  Hanxiao Yin # 1,  Songbo Xie 2,  Linlin Zhang 1,  Xifeng Dong 3,  Hua Ni 1,  Weiwen Bu 1,  Hongbo Ma 1,  Peng Liu 4,  Haiyan Zhu 4,  Rongxia Guo 4,  Lei Sun 2,  Yue Wu 2,  Juan Qin 1,  Baofa Sun 1,  Dengwen Li 1,  Hongbo R Luo 5,  Min Liu 6,  Chenghao Xuan 7,  Jun Zhou 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China.
  • 2 Center for Cell Structure and Function, College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Shandong Normal University, Jinan, China.
  • 3 Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.
  • 4 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
  • 5 Department of Pathology, Department of Laboratory Medicine, Harvard Medical School, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
  • 6 Laboratory of Tissue Homeostasis, Haihe Laboratory of Cell Ecosystem, Tianjin, China.
  • 7 The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • # Contributed equally.
PMID: 37642636 DOI: 10.15252/embr.202256009
Abstract

Hematopoietic stem and progenitor cells (HSPCs) are cells mainly present in the bone marrow and capable of forming mature blood cells. However, the epigenetic mechanisms governing the homeostasis of HSPCs remain elusive. Here, we demonstrate an important role for histone deacetylase 6 (HDAC6) in regulating this process. Our data show that the percentage of HSPCs in HDAC6 knockout mice is lower than in wild-type mice due to decreased HSPC proliferation. HDAC6 interacts with isocitrate dehydrogenase 1 (IDH1) and deacetylates IDH1 at lysine 233. The deacetylation of IDH1 inhibits its catalytic activity and thereby decreases the 5-hydroxymethylcytosine level of ten-eleven translocation 2 (TET2) target genes, changing gene expression patterns to promote the proliferation of HSPCs. These findings uncover a role for HDAC6 and IDH1 in regulating the homeostasis of HSPCs and may have implications for the treatment of hematological diseases.

Keywords

5-hydroxymethylcytosine; HDAC6; HSPCs; IDH1; cell proliferation.

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