1. Direct programming of human pluripotent stem cells into endothelial progenitors with SOX17 and FGF2.
- Author
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Ream MW, Randolph LN, Jiang Y, Chang Y, Bao X, and Lian XL
- Subjects
- Humans, Antigens, CD34 metabolism, Cell Differentiation genetics, Endothelial Cells metabolism, Fibroblast Growth Factor 2 genetics, Fibroblast Growth Factor 2 metabolism, Pluripotent Stem Cells metabolism, SOXF Transcription Factors genetics, SOXF Transcription Factors metabolism
- Abstract
Transcription factors (TFs) are pivotal in guiding stem cell behavior, including their maintenance and differentiation. Using single-cell RNA sequencing, we investigated TFs expressed in endothelial progenitors (EPs) derived from human pluripotent stem cells (hPSCs) and identified upregulated expression of SOXF factors SOX7, SOX17, and SOX18 in the EP population. To test whether overexpression of these factors increases differentiation efficiency, we established inducible hPSC lines for each SOXF factor and found only SOX17 overexpression robustly increased the percentage of cells expressing CD34 and vascular endothelial cadherin (VEC). Conversely, SOX17 knockdown via CRISPR-Cas13d significantly compromised EP differentiation. Intriguingly, we discovered SOX17 overexpression alone was sufficient to generate CD34
+ VEC+ CD31- cells, and, when combined with FGF2 treatment, more than 90% of CD34+ VEC+ CD31+ EP was produced. These cells are capable of further differentiating into endothelial cells. These findings underscore an undiscovered role of SOX17 in programming hPSCs toward an EP lineage, illuminating pivotal mechanisms in EP differentiation., Competing Interests: Declaration of interests The authors declare competing interests. A patent using SOX17 to derive EPs from hPSCs was filed under the inventors of L.N.R., Y.J., and X.L.L., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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