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| Status |
Public on Dec 01, 2017 |
| Title |
Proliferation pause as an early blockade of human cellular reprogramming toward pluripotency |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Human induced Pluripotent Stem cells (iPSCs) can be generated by enforced-expression of OCT3/4, SOX2, KLF4 and c-MYC (OSKM) via intermediate state that is labeled with a surface antigen TRA-1-60. However the event during conversion of somatic cells to TRA-1-60 positive (+) fate by OSKM is still unclear. Here we show that TRA-1-60 (+) cells emerged from ESRG (+) cells with proliferation independent manner. Overcoming the proliferation pausing phase is crucial for further progression of reprogramming. Inactivation of RB pathway is associated with the expansion of early TRA-1-60 (+) cells. Indeed, extended RB activation drastically decreased the proportion of TRA-1-60 (+) cells with marked premature senescence. An RNA-binding protein LIN41 promotes the RB inactivation and facilitates reprogramming efficiency in early stage via post-transcriptional suppression of cycline dependent kinase inhibitor p21. This LIN41/p21/RB axis was invalidated in immortalized cells which showed a resistance to oncogene-induced senescence. Thus, LIN41- mediated RB inactivation promotes to bail out of transient quiescence as a major blockade in initial phase of reprogramming.
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| Overall design |
Reprogrammed cells from five different somatic cell lines, N=90 Human dermal fibroblasts expressing various combination of reprogramming factors, N=48 Human induced Pluripotent Stem cells (iPSCs), N=3 Somatic cell lines N=17
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| Contributor(s) |
Sutou K, Tanabe K, Narita M, Takahashi K |
| Citation(s) |
29641997 |
| Submission date |
Nov 02, 2016 |
| Last update date |
Jun 10, 2019 |
| Contact name |
Kazutoshi Takahashi |
| E-mail(s) |
kazu@cira.kyoto-u.ac.jp
|
| Organization name |
Kyoto University
|
| Department |
Center for iPS Cell Research and Application
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| Street address |
53 Kawahara-cho, Shogoin, Sakyo-ku
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| City |
Kyoto |
| ZIP/Postal code |
606-8507 |
| Country |
Japan |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (158)
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| Relations |
| BioProject |
PRJNA352248 |
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