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Status |
Public on Dec 31, 2022 |
Title |
Direct Induction of hemogenic endothelial progenitors from hPSCs by defined factors revealed by single-cell transcriptome analysis |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Transcription factors play critical roles in stem cell maintenance and differentiation. Using single cell RNA sequencing, we investigated transcription factors expressed in endothelial progenitors differentiated from human pluripotent stem cells (hPSCs) and identified upregulated differential expression of SOXF subgroup members SOX7, SOX17, and SOX18. To test whether overexpression of these factors increases differentiation efficiency, we established inducible hPSC lines and found only SOX17 improved differentiation of CD34+VEC+ cells. Temporal expression analysis of SOX17 and VEC revealed that SOX17 was turned on immediately before VEC, indicating SOX17 may be a causative factor in determining hemogenic endothelial differentiation. Upon Cas13d mediated repression of SOX17, differentiation was significantly abrogated. We found SOX17 forward programming is sufficient to generate more than 50% CD34+VEC+CD73- cells. Further differentiation of SOX17 forward programmed cells generated hematopoietic progenitors that emerged via an endothelial to hematopoietic transition and significantly upregulated definitive hematopoietic transcriptional programs. Our analyses reveal an uncharacterized function of SOX17 in directing hPSCs differentiation towards hematopoietic lineages.
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Overall design |
One sample of hPSCs differentiated to day 5 endothelial progenitors was collected to sequence 2000-3000 cells via scRNAseq
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Web link |
https://doi.org/10.1016/j.stemcr.2024.02.006
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Contributor(s) |
Lian XL, Randolph L |
Citation(s) |
38518781 |
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Submission date |
Nov 13, 2020 |
Last update date |
May 31, 2024 |
Contact name |
Yuqian Jiang |
E-mail(s) |
[email protected]
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Organization name |
PSU
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Street address |
W345 millennium science complex
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City |
University park |
State/province |
PA |
ZIP/Postal code |
16801 |
Country |
USA |
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Platforms (1) |
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Samples (1) |
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Relations |
BioProject |
PRJNA678234 |
SRA |
SRP292479 |