Search

Your search keyword '"Tanabe, Koji"' showing total 2 results
Start Over Author "Tanabe, Koji" Publisher escholarship, university of california
2 results on '"Tanabe, Koji"'

1. MYC Releases Early Reprogrammed Human Cells from Proliferation Pause via Retinoblastoma Protein Inhibition

Author

Rand, Tim A, Sutou, Kenta, Tanabe, Koji, Jeong, Daeun, Nomura, Masaki, Kitaoka, Fumiyo, Tomoda, Emi, Narita, Megumi, Nakamura, Michiko, Nakamura, Masahiro, Watanabe, Akira, Rulifson, Eric, Yamanaka, Shinya, and Takahashi, Kazutoshi

Subjects
Biochemistry and Cell Biology, Biological Sciences, Rare Diseases, 1.1 Normal biological development and functioning, Underpinning research, Antigens, Surface, Cell Line, Cell Proliferation, Cellular Reprogramming, Cyclin-Dependent Kinase Inhibitor p16, Humans, Induced Pluripotent Stem Cells, Kruppel-Like Factor 4, Phosphorylation, Proteoglycans, Proto-Oncogene Proteins c-myc, RNA Interference, RNA, Small Interfering, Retinoblastoma Protein, Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, LIN41, MYC, immortalization, induced pluripotent stem cell, pluripotency, post-transcriptional regulation, proliferation, reprogramming, senescence, Medical Physiology, Biological sciences
Abstract

Here, we report that MYC rescues early human cells undergoing reprogramming from a proliferation pause induced by OCT3/4, SOX2, and KLF4 (OSK). We identified ESRG as a marker of early reprogramming cells that is expressed as early as day 3 after OSK induction. On day 4, ESRG positive (+) cells converted to a TRA-1-60 (+) intermediate state. These early ESRG (+) or TRA-1-60 (+) cells showed a proliferation pause due to increased p16INK4A and p21 and decreased endogenous MYC caused by OSK. Exogenous MYC did not enhance the appearance of initial reprogramming cells but instead reactivated their proliferation and improved reprogramming efficiency. MYC increased expression of LIN41, which potently suppressed p21 post-transcriptionally. MYC suppressed p16 INK4A. These changes inactivated retinoblastoma protein (RB) and reactivated proliferation. The RB-regulated proliferation pause does not occur in immortalized fibroblasts, leading to high reprogramming efficiency even without exogenous MYC.

Published
2018

2. The let-7/LIN-41 Pathway Regulates Reprogramming to Human Induced Pluripotent Stem Cells by Controlling Expression of Prodifferentiation Genes

Author

Worringer, Kathleen A, Rand, Tim A, Hayashi, Yohei, Sami, Salma, Takahashi, Kazutoshi, Tanabe, Koji, Narita, Megumi, Srivastava, Deepak, and Yamanaka, Shinya

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Genetics, Stem Cell Research, Regenerative Medicine, Blotting, Western, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cellular Reprogramming, Early Growth Response Protein 1, Fluorescent Antibody Technique, Humans, Induced Pluripotent Stem Cells, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors, MicroRNAs, Octamer Transcription Factor-3, Proto-Oncogene Proteins c-myc, RNA, Messenger, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Reprogramming differentiated cells into induced pluripotent stem cells (iPSCs) promotes a broad array of cellular changes. Here we show that the let-7 family of microRNAs acts as an inhibitory influence on the reprogramming process through a regulatory pathway involving prodifferentiation factors, including EGR1. Inhibiting let-7 in human cells promotes reprogramming to a comparable extent to c-MYC when combined with OCT4, SOX2, and KLF4, and persistence of let-7 inhibits reprogramming. Inhibiting let-7 during reprogramming leads to an increase in the level of the let-7 target LIN-41/TRIM71, which in turn promotes reprogramming and is important for overcoming the let-7 barrier to reprogramming. Mechanistic studies revealed that LIN-41 regulates a broad array of differentiation genes, and more specifically, inhibits translation of EGR1 through binding its cognate mRNA. Together our findings outline a let-7-based pathway that counteracts the activity of reprogramming factors through promoting the expression of prodifferentiation genes.

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results