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| Status |
Public on Apr 26, 2017 |
| Title |
Lineage specific differentiation is influenced by state of human pluripotency [methylation] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Human pluripotent stem cells (hPSCs) have been reported in naïve and primed states. However, the ability of human PSCs to generate mature cell types is the only imperative property for translational utility. Here, we reveal that the naïve state enhances self-renewal capacity while restricting lineage differentiation in vitro to neural default fate. Gene expression analyses indicate expression of multiple lineage associated transcripts in naïve hPSCs and thus failed to predict biased functional differentiation. Naïve hPSCs can be converted to primed allowing recovery of multilineage differentiation over long serial passage or immediately through suppression of OCT4 but not NANOG. To this end, we identified chemical inhibitors of OCT4 expression that acutely restore naïve hPSC differentiation. Our study identifies unique cell fate features and critical restrictions in human pluripotent states, and provides an approach to overcome these barriers that harness both efficient naïve hPSC growth whilst maintaining in vitro differentiation capacities essential for hPSC applications.
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| Overall design |
hPSC lines were transduced with shRNA lentiviruses in order to assess the effects of reducing NANOG and OCT4 gene expression on differention in the naïve state. shRNA expressing cells were sorted and then genomic DNA was extracted in order to assess methylation status.
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| Contributor(s) |
Lee JH, Bhatia M |
| Citation(s) |
28380358 |
| Submission date |
Feb 28, 2017 |
| Last update date |
Jan 20, 2019 |
| Contact name |
Mickie Bhatia |
| E-mail(s) |
mbhatia@mcmaster.ca
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| Organization name |
McMaster University
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| Department |
Stem Cell and Cancer Research Institute (SCC-RI)
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| Street address |
1200 Main Street West
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| City |
Hamilton |
| State/province |
Ontario |
| ZIP/Postal code |
L8N 3Z5 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (8)
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| GSM2515899 |
human pluripotent stem cells, primed, control, 1 |
| GSM2515900 |
human pluripotent stem cells, primed, control, 2 |
| GSM2515901 |
human pluripotent stem cells, naïve, control, 1 |
| GSM2515902 |
human pluripotent stem cells, naïve, control, 2 |
| GSM2515903 |
human pluripotent stem cells, naïve, shPOU5F1, 1 |
| GSM2515904 |
human pluripotent stem cells, naïve, shPOU5F1, 2 |
| GSM2515905 |
human pluripotent stem cells, naïve, shNANOG, 1 |
| GSM2515906 |
human pluripotent stem cells, naïve, shNANOG, 2 |
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| This SubSeries is part of SuperSeries: |
| GSE95505 |
Lineage specific differentiation is influenced by state of human pluripotency |
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| Relations |
| BioProject |
PRJNA377404 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE95531_Matrix_signal_intensities_JH_LIF2i_2017_Methylation_.txt.gz |
42.4 Mb |
(ftp)(http) |
TXT |
| GSE95531_RAW.tar |
273.5 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
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