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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 |
Expression profiling by array
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| 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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| Overall design |
The gene expression changes when TCF7 is knocked-down by shRNA in Lin-SCA+CD34+ cells were identified by microarray analysis of one control and two experimental samples.
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| Contributor(s) |
Wu JQ, Seay M, Schulz V, Tuck D, Lian J, Hariharan M, Shi M, Ye Z, Du J, Gerstein M, Snyder M, Weissman S |
| Citation(s) |
22412390 |
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| Submission date |
Jun 17, 2011 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Vince Schulz |
| E-mail(s) |
vincent.schulz@yale.edu
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| Organization name |
Yale University
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| Department |
Department of Pediatrics
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| Lab |
Gallagher
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| Street address |
333 Cedar St. LMP 4085
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| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06519 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA144003 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30068_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE30068_non-normalized.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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