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| Status |
Public on Mar 30, 2012 |
| Title |
TCF7 is a key regulator of the switch of self-renewal and differentiation in a multipotential hematopoietic cell line |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
A critical problem in biology is understanding how cells choose between self-renewal and differentiation. To generate a comprehensive view of the mechanisms controlling early hematopoietic precursor self-renewal and differentiation, we used systems-based approaches and murine EML multipotential hematopoietic precursor cells as a primary model. EML cells give rise to a mixture of self-renewing Lin-SCA+CD34+ cells and partially differentiated non-renewing Lin-SCA-CD34- cells in a cell autonomous fashion. We identified and validated the HMG box protein TCF7 as a key regulator in this self-renewal/differentiation switch, and it operates in the absence of canonical Wnt signaling. We found that TCF7 is the most downregulated transcription factor when CD34+ cells switch into CD34- cells using RNA-Seq. We subsequently identified the target genes bound by TCF7 using ChIP-Seq. We show that TCF7 binds to Runx1 (Aml1) promoter region, and RUNX1 and TCF7 co-regulate. Gene Set Enrichment Analysis suggests that TCF7 primarily acts as a positive regulator of genes preferentially expressed in CD34+ cells. Consistent with this possibility, knocking-down TCF7 represses many up-regulated genes in Lin-CD34+ cells. Finally a network of up-regulated transcription factors of CD34+ cells which defines the self-renewing state was constructed. These studies in EML cells demonstrate fundamental cell-intrinsic properties of the switch between self-renewal and differentiation, and yield valuable insights for manipulating HSCs and other differentiating systems.
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| |
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| Overall design |
Examining the transcription factor binding targets of TCF7 and RUNX1.
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| |
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| Contributor(s) |
Wu JQ, Seay M, Hariharan M, Snyder M, Weissman S |
| Citation(s) |
22412390 |
| Submission date |
Aug 04, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Jiaqian Wu |
| E-mail(s) |
jiaqian2009.wu@gmail.com
|
| Organization name |
Stanford University
|
| Street address |
1501 California Avenue
|
| City |
PALO ALTO |
| ZIP/Postal code |
94306 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (5)
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| Relations |
| SRA |
SRP007879 |
| BioProject |
PRJNA146073 |
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