HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells.
Jia YangYang LiuHanxiao YinSongbo XieLinlin ZhangXifeng DongHua NiWeiwen BuHongbo MaPeng LiuHaiyan ZhuRongxia GuoLei SunYue WuJuan QinBaofa SunDengwen LiHongbo R LuoMin LiuChenghao XuanJun ZhouPublished in: EMBO reports (2023)
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.
Keyphrases
- wild type
- histone deacetylase
- gene expression
- induced apoptosis
- bone marrow
- low grade
- signaling pathway
- cell cycle arrest
- dna methylation
- mesenchymal stem cells
- genome wide
- binding protein
- type diabetes
- cell proliferation
- big data
- machine learning
- skeletal muscle
- high grade
- deep learning
- combination therapy
- transcription factor
- high fat diet induced
- replacement therapy
- data analysis
- insulin resistance