より優れた人工血管のための3つの錠前を破るために必要な2つの鍵(Two keys needed to crack three locks for better engineered blood vessels)

2024-03-22

2024-03-21 ペンシルベニア州立大学(PennState)

ペンシルベニア州立大学の研究チームは、幹細胞から作られた血管が、薬物候補が脳に移行できるかどうかをスクリーニングするプラットフォームや心臓移植をサポートするための血管組織を提供できる可能性があると報告しました。彼らは特定の分子信号を発見し、これにより幹細胞が内皮細胞に効率的に成熟することが可能になりました。この成果はStem Cell Reports誌に掲載されました。

<関連情報>

SOX17とFGF2を用いてヒト多能性幹細胞を内皮前駆細胞に直接プログラミングする Direct programming of human pluripotent stem cells into endothelial progenitors with SOX17 and FGF2

Michael W. Ream ,Lauren N. Randolph,Yuqian Jiang,Yun Chang,Xiaoping Bao,Xiaojun Lance Lian,
Stem Cell Reports Published:March 21, 2024
DOI:https://doi.org/10.1016/j.stemcr.2024.02.006

Highlights

•scRNA-seq analysis of EPs identifies differential expression of three SOXF factors

•Overexpression of SOX17 can enhance CHIR99021-mediated EP differentiation

•Overexpression of SOX17 alone is sufficient to generate 50% CD34⁺VEC⁺ EPs

•FGF2 can enhance EP programming via SOX17, yielding 90% CD31⁺CD34⁺VEC⁺ EPs

Summary

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.