Open AccessPDK1 plays a vital role on hematopoietic stem cell function
Author(s) -
Tianyuan Hu,
Cong Liu,
Le Wang,
Yingchi Zhang,
Lincai Peng,
Hui Cheng,
Yajing Chu,
Weili Wang,
Hideo Ema,
Yingdai Gao,
Zhenyu Ju,
Zhongzhou Yang,
Xiaomin Wang,
Tao Cheng,
Weiping Yuan
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-05213-3
Subject(s) - haematopoiesis , microbiology and biotechnology , protein kinase b , pi3k/akt/mtor pathway , stem cell , hematopoietic stem cell , biology , progenitor cell , kinase , regulator , signal transduction , gene , genetics
3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway that have been shown to play key roles in the functional development of B and T cells via activation of AGC protein kinases during hematopoiesis. However, the role of PDK1 in HSCs has not been fully defined. Here we specifically deleted the PDK1 gene in the hematopoietic system and found that PDK1 -deficient HSCs exhibited impaired function and defective lineage commitment abilities. Lack of PDK1 caused HSCs to be less quiescent and to produce a higher number of phenotypic HSCs and fewer progenitors. PDK1 -deficient HSCs were also unable to reconstitute the hematopoietic system. Notably, HSC function was more dependent on PDK1 than on mTORC2, which indicates that PDK1 plays a dominant role in the Akt-mediated regulation of HSC function. PDK1 -deficient HSCs also exhibited reduced ROS levels, and treatment of PDK1 -deficient HSCs with L-butathioninesulfoximine in vitro elevated the low ROS level and promoted colony formation. Therefore, PDK1 appears to contribute to HSC function partially via regulating ROS levels.