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| Status |
Public on Nov 01, 2020 |
| Title |
The T-box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors [ATAC-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Extra-embryonic mesoderm (ExM), the earliest cells that traverse through the primitive streak, give rise to the endothelium as well as hematopoietic progenitors in the developing yolk-sac (YS). How a specific subset of ExM becomes committed to a hematopoietic fate remains unclear. Here we report that Eomesodermin (Eomes), a T-box transcription factor, is transiently expressed in ExM progenitors that generate virtually all YS hematopoietic and endothelial cells. Using an embryonic stem cell (ESC) differentiation system, we find that Eomes activity is essential for the production of primitive erythrocytes and for the normal development of Runx1+ HE that generates the definitive hematopoietic progenitors. RNA-Seq and ATAC-Seq experiments reveal that Eomes governs the accessibility of numerous hematopoietic enhancers that SCL normally utilizes to specify primitive erythrocytes and HE in Flk-1hi/PdgfRa- hematovascular mesoderm. ChIP-seq experiments suggest that Eomes coordinates the development of hemogenic competent mesoderm in the context of Activin/Nodal and Tead-Yap signaling. Finally, single-cell- RNA-seq (scRNAseq) shows that in the absence of Eomes function diversion towards an endothelial rather than hematopoietic fate occurs after the initial specification of Flk-1+/SCL+ hematovascular mesoderm. Collectively, these experiments demonstrate that Eomes sits at the top of the transcriptional hierarchy, functioning upstream of Runx1 expression and SCL functional activity, and promotes hemogenic competence of the entire YS mesodermal lineage.
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| Overall design |
Tn5-accessible chromatin profiles of wild type and Eomes-null day 4 Flk-1hi/PdfgRa- EB cells were generated by deep sequencing in biological triplicate using Illumina HiSeq4000.
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| Contributor(s) |
Harland LT, Simon CS, Senft AD, Costello I, Greder L, Bikoff EK, Porcher C, de Bruijn M, Robertson EJ |
| Citation(s) |
33420489 |
| |
| Submission date |
Nov 06, 2019 |
| Last update date |
Apr 06, 2021 |
| Contact name |
Luke Thomas Gilbert Harland |
| E-mail(s) |
luke.harland@path.ox.ac.uk
|
| Organization name |
Oxford University
|
| Department |
Sir William Dunn School of Pathology
|
| Lab |
Elizabeth Robertson
|
| Street address |
South Parks Road
|
| City |
Oxford |
| ZIP/Postal code |
OX1 3RE |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE140005 |
The T-box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors |
|
| Relations |
| BioProject |
PRJNA588505 |
| SRA |
SRP229402 |
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