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| Status |
Public on Jun 07, 2020 |
| Title |
A PIANO (Proper, Insufficient, Aberrant, and NO reprogramming) response to the Yamanaka factors in the initial stages of human iPSC reprogramming |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Yamanaka reprogramming is revolutionary but inefficient, slow and stochastic. The underlying molecular events for these mixed outcomes of iPSC reprogramming is still unclear. Previous studies about transcriptional responses to reprogramming overlooked human reprogramming, and are compromised by the fact that only a rare population proceeds towards pluripotency and a significant amount of the collected transcriptional data may not represent the positive reprogramming. We recently developed a concept of reprogramome, which allows one to study the early transcriptional responses to the Yamanaka factors in the perspective of reprogramming legitimacy of a gene response to reprogramming. Using RNA-seq, this study scored 579 genes successfully reprogrammed within 48 hours, indicating the potency of the reprogramming factors. This report also tallied 438 genes reprogrammed significantly but insufficiently up to 72 hours, indicating a positive drive with some inadequacy of the Yamanaka factors. In addition, 953 member genes within the reprogramome were transcriptionally irresponsive to reprogramming, showing the inability of the reprogramming factors to directly act on these genes. Furthermore, there were 305 genes undergoing six types of aberrant reprogramming: over, wrong, and unwanted up- or down- reprogramming, revealing significant negative impacts of the Yamanaka factors. The mixed findings about the initial transcriptional responses to the reprogramming factors shed new insights into the robustness as well as limitations of the Yamanaka factors.
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| Overall design |
Human embryonic stem cell (n=3) expression were compared to human fibroblasts (n=4) to define the reprogramome. Human fibroblasts BJ cells with and without transduction with lentiviral GFP were RNA-sequenced, the their transcriptomes were compared with the human fibroblasts transduced with the Yamanaka factors, OCT4, SOX2, KLF4 and c-MYC. Different patterns of transcirptional responses to reprogramming were identified with the perspective of reprogramming legitimacy.
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| Contributor(s) |
Hu K |
| Citation(s) |
32370214, 33203179 |
| Submission date |
Apr 06, 2020 |
| Last update date |
Dec 08, 2020 |
| Contact name |
Kejin Hu |
| E-mail(s) |
kejinhu@uab.edu
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| Phone |
205-934-4700
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| Organization name |
University of Alabama at Birmingham
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| Department |
Biochemistry
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| Lab |
Hu Lab
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| Street address |
1825 University Boulevard
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| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35294 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA623357 |
| SRA |
SRP255395 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148158_normalized_counts_MS2.csv.gz |
2.4 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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