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Status |
Public on May 13, 2019 |
Title |
Transcription factor NKX3-1 is required for reprogramming to pluripotency and can replace OCT4 in mouse and human iPSC induction [RNA-seq] |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Resolution of early molecular events preceding endogenous OCT4 activation is critical to understanding the mechanism of reprogramming somatic cells to induced pluripotent stem cells (iPSCs), yet capturing transient regulators at the onset of reprogramming is difficult in heterogeneous populations of asynchronously reprogramming fibroblasts following four-factor transduction. To address this need, we used a heterokaryon system to identify an early and transiently expressed homeobox transcription factor, NKX3-1. Upon knockdown of NKX3-1, iPSC reprogramming is abrogated. Further, we identify that NKX3-1 functions downstream of the IL6-STAT3 regulatory network to activate endogenous OCT4. Importantly, we show that NKX3-1 can substitute for exogenous OCT4 to reprogram both mouse and human fibroblasts at comparable efficiencies generate fully pluripotent stem cells. Our findings establish an essential role for NKX3-1, previously known as a prostate-specific tumor suppressor, in iPSC reprogramming.
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Overall design |
RNA-seq timecourse of heterokaryon reprogramming
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Contributor(s) |
Mai T, Brady JJ, Blau HM |
Citation(s) |
30013107 |
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Submission date |
Sep 05, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Thach Mai |
E-mail(s) |
tamai@stanford.edu
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Organization name |
Stanford University
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Street address |
269 Campus Dr
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City |
Stanford |
ZIP/Postal code |
94305 |
Country |
USA |
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Platforms (4)
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GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL16512 |
Illumina HiSeq 2000 (Homo sapiens; Mus musculus) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (25)
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This SubSeries is part of SuperSeries: |
GSE103536 |
Transcription factor NKX3-1 is required for reprogramming to pluripotency and can replace OCT4 in mouse and human iPSC induction |
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Relations |
BioProject |
PRJNA401768 |
SRA |
SRP116963 |