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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05213-3 |
| _version_ | 1828972015658205184 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:19:46Z |
| format | Article |
| id | doaj.art-0c1327a89dcc4eef9b1ed592b725aa6d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:19:46Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0c1327a89dcc4eef9b1ed592b725aa6d2022-12-21T22:59:57ZengNature PortfolioScientific Reports2045-23222017-07-017111010.1038/s41598-017-05213-3PDK1 plays a vital role on hematopoietic stem cell functionTianyuan Hu0Cong Li1Le Wang2Yingchi Zhang3Luyun Peng4Hui Cheng5Yajing Chu6Weili Wang7Hideo Ema8Yingdai Gao9Zhenyu Ju10Zhongzhou Yang11Xiaomin Wang12Tao Cheng13Weiping Yuan14State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Ageing, Hangzhou Normal UniversityMinistry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing UniversityState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract 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.https://doi.org/10.1038/s41598-017-05213-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | PDK1 plays a vital role on hematopoietic stem cell function |
| title_sort | pdk1 plays a vital role on hematopoietic stem cell function |
| url | https://doi.org/10.1038/s41598-017-05213-3 |
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