PDK1 plays a vital role on hematopoietic stem cell function
Abstract 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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0c1327a89dcc4eef9b1ed592b725aa6d |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0c1327a89dcc4eef9b1ed592b725aa6d |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0c1327a89dcc4eef9b1ed592b725aa6d2021-12-02T11:53:10ZPDK1 plays a vital role on hematopoietic stem cell function10.1038/s41598-017-05213-32045-2322https://doaj.org/article/0c1327a89dcc4eef9b1ed592b725aa6d2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05213-3https://doaj.org/toc/2045-2322Abstract 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.Tianyuan HuCong LiLe WangYingchi ZhangLuyun PengHui ChengYajing ChuWeili WangHideo EmaYingdai GaoZhenyu JuZhongzhou YangXiaomin WangTao ChengWeiping YuanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Tianyuan Hu Cong Li Le Wang Yingchi Zhang Luyun Peng Hui Cheng Yajing Chu Weili Wang Hideo Ema Yingdai Gao Zhenyu Ju Zhongzhou Yang Xiaomin Wang Tao Cheng Weiping Yuan PDK1 plays a vital role on hematopoietic stem cell function |
| description |
Abstract 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. |
| format |
article |
| author |
Tianyuan Hu Cong Li Le Wang Yingchi Zhang Luyun Peng Hui Cheng Yajing Chu Weili Wang Hideo Ema Yingdai Gao Zhenyu Ju Zhongzhou Yang Xiaomin Wang Tao Cheng Weiping Yuan |
| author_facet |
Tianyuan Hu Cong Li Le Wang Yingchi Zhang Luyun Peng Hui Cheng Yajing Chu Weili Wang Hideo Ema Yingdai Gao Zhenyu Ju Zhongzhou Yang Xiaomin Wang Tao Cheng Weiping Yuan |
| author_sort |
Tianyuan Hu |
| title |
PDK1 plays a vital role on hematopoietic stem cell function |
| title_short |
PDK1 plays a vital role on hematopoietic stem cell function |
| title_full |
PDK1 plays a vital role on hematopoietic stem cell function |
| title_fullStr |
PDK1 plays a vital role on hematopoietic stem cell function |
| title_full_unstemmed |
PDK1 plays a vital role on hematopoietic stem cell function |
| title_sort |
pdk1 plays a vital role on hematopoietic stem cell function |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/0c1327a89dcc4eef9b1ed592b725aa6d |
| work_keys_str_mv |
AT tianyuanhu pdk1playsavitalroleonhematopoieticstemcellfunction AT congli pdk1playsavitalroleonhematopoieticstemcellfunction AT lewang pdk1playsavitalroleonhematopoieticstemcellfunction AT yingchizhang pdk1playsavitalroleonhematopoieticstemcellfunction AT luyunpeng pdk1playsavitalroleonhematopoieticstemcellfunction AT huicheng pdk1playsavitalroleonhematopoieticstemcellfunction AT yajingchu pdk1playsavitalroleonhematopoieticstemcellfunction AT weiliwang pdk1playsavitalroleonhematopoieticstemcellfunction AT hideoema pdk1playsavitalroleonhematopoieticstemcellfunction AT yingdaigao pdk1playsavitalroleonhematopoieticstemcellfunction AT zhenyuju pdk1playsavitalroleonhematopoieticstemcellfunction AT zhongzhouyang pdk1playsavitalroleonhematopoieticstemcellfunction AT xiaominwang pdk1playsavitalroleonhematopoieticstemcellfunction AT taocheng pdk1playsavitalroleonhematopoieticstemcellfunction AT weipingyuan pdk1playsavitalroleonhematopoieticstemcellfunction |
| _version_ |
1718394849223245824 |