The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling
Abstract Deficiency of P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of P18 overexpression, which is involved in the inhibitory effects of RUNX1b at the early stage of hematopoiesis, have not...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-03263-2 |
| _version_ | 1819009245553623040 |
|---|---|
| author | Danying Yi Lijiao Zhu Yuanling Liu Jiahui Zeng Jing Chang Wencui Sun Jiawen Teng Yonggang Zhang Yong Dong Xu Pan Yijin Chen Ya Zhou Mowen Lai Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma |
| author_facet | Danying Yi Lijiao Zhu Yuanling Liu Jiahui Zeng Jing Chang Wencui Sun Jiawen Teng Yonggang Zhang Yong Dong Xu Pan Yijin Chen Ya Zhou Mowen Lai Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma |
| author_sort | Danying Yi |
| collection | DOAJ |
| description | Abstract Deficiency of P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of P18 overexpression, which is involved in the inhibitory effects of RUNX1b at the early stage of hematopoiesis, have not been examined in detail. In this study, we established inducible P18/hESC lines and monitored the effects of P18 overexpression on hematopoietic differentiation. Induction of P18 from day 0 (D0) dramatically decreased production of CD34highCD43− cells and derivative populations, but not that of CD34lowCD43− cells, changed the cell cycle status and apoptosis of KDR+ cells and downregulated the key hematopoietic genes at D4, which might cause the severe blockage of hematopoietic differentiation at the early stage. By contrast, induction of P18 from D10 dramatically increased production of classic hematopoietic populations and changed the cell cycle status and apoptosis of CD45+ cells at D14. These effects can be counteracted by inhibition of TGF-β or NF-κB signaling respectively. This is the first evidence that P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs). |
| first_indexed | 2024-12-21T00:53:18Z |
| format | Article |
| id | doaj.art-1cb9ecc2adf1459badca56e32165f068 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T00:53:18Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1cb9ecc2adf1459badca56e32165f0682022-12-21T19:21:22ZengNature PortfolioScientific Reports2045-23222021-12-0111111310.1038/s41598-021-03263-2The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signalingDanying Yi0Lijiao Zhu1Yuanling Liu2Jiahui Zeng3Jing Chang4Wencui Sun5Jiawen Teng6Yonggang Zhang7Yong Dong8Xu Pan9Yijin Chen10Ya Zhou11Mowen Lai12Qiongxiu Zhou13Jiaxin Liu14Bo Chen15Feng Ma16Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC)Abstract Deficiency of P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of P18 overexpression, which is involved in the inhibitory effects of RUNX1b at the early stage of hematopoiesis, have not been examined in detail. In this study, we established inducible P18/hESC lines and monitored the effects of P18 overexpression on hematopoietic differentiation. Induction of P18 from day 0 (D0) dramatically decreased production of CD34highCD43− cells and derivative populations, but not that of CD34lowCD43− cells, changed the cell cycle status and apoptosis of KDR+ cells and downregulated the key hematopoietic genes at D4, which might cause the severe blockage of hematopoietic differentiation at the early stage. By contrast, induction of P18 from D10 dramatically increased production of classic hematopoietic populations and changed the cell cycle status and apoptosis of CD45+ cells at D14. These effects can be counteracted by inhibition of TGF-β or NF-κB signaling respectively. This is the first evidence that P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs).https://doi.org/10.1038/s41598-021-03263-2 |
| spellingShingle | Danying Yi Lijiao Zhu Yuanling Liu Jiahui Zeng Jing Chang Wencui Sun Jiawen Teng Yonggang Zhang Yong Dong Xu Pan Yijin Chen Ya Zhou Mowen Lai Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling Scientific Reports |
| title | The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling |
| title_full | The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling |
| title_fullStr | The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling |
| title_full_unstemmed | The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling |
| title_short | The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-β and NF-κB signaling |
| title_sort | distinct effects of p18 overexpression on different stages of hematopoiesis involve tgf β and nf κb signaling |
| url | https://doi.org/10.1038/s41598-021-03263-2 |
| work_keys_str_mv | AT danyingyi thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT lijiaozhu thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yuanlingliu thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jiahuizeng thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jingchang thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT wencuisun thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jiawenteng thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yonggangzhang thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yongdong thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT xupan thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yijinchen thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yazhou thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT mowenlai thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT qiongxiuzhou thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jiaxinliu thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT bochen thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT fengma thedistincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT danyingyi distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT lijiaozhu distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yuanlingliu distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jiahuizeng distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jingchang distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT wencuisun distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jiawenteng distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yonggangzhang distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yongdong distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT xupan distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yijinchen distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT yazhou distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT mowenlai distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT qiongxiuzhou distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT jiaxinliu distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT bochen distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling AT fengma distincteffectsofp18overexpressionondifferentstagesofhematopoiesisinvolvetgfbandnfkbsignaling |