2. Academic Validation
  3. Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability

Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability

  • Cell Death Dis. 2019 Mar 20;10(4):271. doi: 10.1038/s41419-019-1502-8.
Zhiyan Zhan 1,  Lili Song 1,  Weiwei Zhang 2,  Haihui Gu 3,  Haizi Cheng 4,  Yingwen Zhang 1,  Yi Yang 1,  Guangzhen Ji 5,  Haizhong Feng 6,  Tao Cheng 7 8 9,  Yanxin Li 10
Affiliations

Affiliations

  • 1 Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology & Oncology, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 2 State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 3 Department of Blood Transfusion, Changhai Hospital, Shanghai, 200433, China.
  • 4 Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, 5117 Center Avenue, Pittsburgh, PA, 15213, USA.
  • 5 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
  • 6 State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. fenghaizhong@sjtu.edu.cn.
  • 7 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. chengtao@ihcams.ac.cn.
  • 8 Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China. chengtao@ihcams.ac.cn.
  • 9 Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China. chengtao@ihcams.ac.cn.
  • 10 Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology & Oncology, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. liyanxin@scmc.com.cn.
PMID: 30894510 DOI: 10.1038/s41419-019-1502-8
Abstract

Mechanisms underlying the generation of induced pluripotent stem cells (iPSC) and keeping iPSC stability remain to be further defined. Accumulated evidences showed that iPSC reprogramming may be controlled by the cell-division-rate-dependent model. Here we reported effects of absence of mouse p27 or p18 on iPSC generation efficiency and genomic stability. Expression levels of cyclin-dependent kinases inhibitors (CDKIs), p21, p27, and p18 decreased during iPSC reprogramming. Like p21 loss, p27 or p18 deficiency significantly promoted efficiency of iPSC generation, whereas ectopic expression of p27, p18, or treatment with CDK2 or CDK4 inhibitors repressed the reprogramming rate, suggesting that CDKIs-regulated iPSC reprogramming is directly related with their functions as CDK inhibitors. However, unlike p21 deletion, absence of p27 or p18 did not increase DNA damage or chromosomal aberrations during iPSC reprogramming and at iPSC stage. Our data not only support that cell cycle regulation is critical for iPSC reprogramming, but also reveal the distinction of CDKIs in somatic cell reprogramming.

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