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The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-ß and NF-κB signaling.
Yi, Danying; Zhu, Lijiao; Liu, Yuanling; Zeng, Jiahui; Chang, Jing; Sun, Wencui; Teng, Jiawen; Zhang, Yonggang; Dong, Yong; Pan, Xu; Chen, Yijin; Zhou, Ya; Lai, Mowen; Zhou, Qiongxiu; Liu, Jiaxin; Chen, Bo; Ma, Feng.
Afiliación
  • Yi D; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Zhu L; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Liu Y; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Zeng J; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Chang J; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Sun W; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Teng J; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Zhang Y; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Dong Y; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Pan X; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Chen Y; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Zhou Y; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Lai M; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Zhou Q; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Liu J; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China.
  • Chen B; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China. Bo_Chen@ibt.pumc.edu.cn.
  • Ma F; Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, 610052, China. mafeng@ibt.pumc.edu.cn.
Sci Rep ; 11(1): 24014, 2021 12 14.
Article en En | MEDLINE | ID: mdl-34907231
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-ß or NF-κB signaling respectively. This is the first evidence that P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs).
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Diferenciación Celular / Regulación de la Expresión Génica / FN-kappa B / Factor de Crecimiento Transformador beta / Inhibidor p18 de las Quinasas Dependientes de la Ciclina / Células Madre Embrionarias Humanas Límite: Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Diferenciación Celular / Regulación de la Expresión Génica / FN-kappa B / Factor de Crecimiento Transformador beta / Inhibidor p18 de las Quinasas Dependientes de la Ciclina / Células Madre Embrionarias Humanas Límite: Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido