RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest
p15INK4b (cyclin-dependent kinase inhibitor 2B, CDKN2B, p15), a cyclin-dependent kinase inhibitor (CKI) belonging to the INK4 family, plays an important role in hematopoiesis. Its expression level was positively related to the blockage effects of RUNX1b at the early stage. Experiments using human em...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-04-01
|
| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506122000435 |
| _version_ | 1818287609119506432 |
|---|---|
| author | Wencui Sun Danying Yi Lijiao Zhu Jiahui Zeng Yuanling Liu Jing Chang Jiawen Teng Yonggang Zhang Yong Dong Xu Pan Yijin Chen Ya Zhou Mowen Lai Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma |
| author_facet | Wencui Sun Danying Yi Lijiao Zhu Jiahui Zeng Yuanling Liu Jing Chang Jiawen Teng Yonggang Zhang Yong Dong Xu Pan Yijin Chen Ya Zhou Mowen Lai Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma |
| author_sort | Wencui Sun |
| collection | DOAJ |
| description | p15INK4b (cyclin-dependent kinase inhibitor 2B, CDKN2B, p15), a cyclin-dependent kinase inhibitor (CKI) belonging to the INK4 family, plays an important role in hematopoiesis. Its expression level was positively related to the blockage effects of RUNX1b at the early stage. Experiments using human embryonic stem cell (hESC) lines with inducible p15 expression suggested that p15 overexpression can significantly decrease the proportion of KDR+ cells in S and G2-M stages 4 days after induction from day 0. Moreover, p15 overexpression from the early stage can decrease production of CD34highCD43− cells and their derivative populations, but not CD34lowCD43− cells. These effects were weakened if induction was delayed and disappeared if induction started after day 6. All these effects were counteracted by inhibition of TGF-β signaling. TGF-β1 stimulation elicited similar effects as p15 overexpression. RUNX1 overexpression and activation of the TGF-β signaling pathway upregulate the expression of p15, which is partially responsible for blockade of hematopoiesis and relevant to a change in the cell cycle status. However, it is possible that other mechanisms are involved in the regulation of hematopoiesis. |
| first_indexed | 2024-12-13T01:43:12Z |
| format | Article |
| id | doaj.art-95025074c96e4ffd91b5ec4590a113cb |
| institution | Directory Open Access Journal |
| issn | 1873-5061 |
| language | English |
| last_indexed | 2024-12-13T01:43:12Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-95025074c96e4ffd91b5ec4590a113cb2022-12-22T00:03:41ZengElsevierStem Cell Research1873-50612022-04-0160102694RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrestWencui Sun0Danying Yi1Lijiao Zhu2Jiahui Zeng3Yuanling Liu4Jing Chang5Jiawen Teng6Yonggang Zhang7Yong Dong8Xu Pan9Yijin Chen10Ya Zhou11Mowen Lai12Qiongxiu Zhou13Jiaxin Liu14Bo Chen15Feng Ma16Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, ChinaInstitute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China; Corresponding authors at: Center for Stem Cell Research and Application, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, Sichuan 610052, China.Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China; State Key Laboratory of Experimental Hematology, CAMS & PUMC, Tianjin 300020, China; Corresponding authors at: Center for Stem Cell Research and Application, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, Sichuan 610052, China.p15INK4b (cyclin-dependent kinase inhibitor 2B, CDKN2B, p15), a cyclin-dependent kinase inhibitor (CKI) belonging to the INK4 family, plays an important role in hematopoiesis. Its expression level was positively related to the blockage effects of RUNX1b at the early stage. Experiments using human embryonic stem cell (hESC) lines with inducible p15 expression suggested that p15 overexpression can significantly decrease the proportion of KDR+ cells in S and G2-M stages 4 days after induction from day 0. Moreover, p15 overexpression from the early stage can decrease production of CD34highCD43− cells and their derivative populations, but not CD34lowCD43− cells. These effects were weakened if induction was delayed and disappeared if induction started after day 6. All these effects were counteracted by inhibition of TGF-β signaling. TGF-β1 stimulation elicited similar effects as p15 overexpression. RUNX1 overexpression and activation of the TGF-β signaling pathway upregulate the expression of p15, which is partially responsible for blockade of hematopoiesis and relevant to a change in the cell cycle status. However, it is possible that other mechanisms are involved in the regulation of hematopoiesis.http://www.sciencedirect.com/science/article/pii/S1873506122000435RUNX1/AML1TGF-β signaling pathwayHematopoiesisHuman embryonic stem cell (hESC)P15Cell cycle |
| spellingShingle | Wencui Sun Danying Yi Lijiao Zhu Jiahui Zeng Yuanling Liu Jing Chang Jiawen Teng Yonggang Zhang Yong Dong Xu Pan Yijin Chen Ya Zhou Mowen Lai Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest Stem Cell Research RUNX1/AML1 TGF-β signaling pathway Hematopoiesis Human embryonic stem cell (hESC) P15 Cell cycle |
| title | RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest |
| title_full | RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest |
| title_fullStr | RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest |
| title_full_unstemmed | RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest |
| title_short | RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest |
| title_sort | runx1 overexpression triggers tgf β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest |
| topic | RUNX1/AML1 TGF-β signaling pathway Hematopoiesis Human embryonic stem cell (hESC) P15 Cell cycle |
| url | http://www.sciencedirect.com/science/article/pii/S1873506122000435 |
| work_keys_str_mv | AT wencuisun runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT danyingyi runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT lijiaozhu runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT jiahuizeng runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT yuanlingliu runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT jingchang runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT jiawenteng runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT yonggangzhang runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT yongdong runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT xupan runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT yijinchen runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT yazhou runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT mowenlai runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT qiongxiuzhou runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT jiaxinliu runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT bochen runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest AT fengma runx1overexpressiontriggerstgfbsignalingtoupregulatep15andtherebyblocksearlyhematopoiesisbyinducingcellcyclearrest |