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化学定义和没有生长因子的系统,用于高效的内皮诱导人类多能干细胞

Zhiju Zhao¹, Fanzhu Zeng², Yage Nie³

¹Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong 510080, China; Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangdong 510080, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics, The Chinese University of Hong Kong, New Territories, Hong Kong SAR 999077, China; Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR 999077, China.

Stem cell reports

|December 27, 2024

概括

研究人员开发了一种新的,具有成本效益的方法,只使用四个小分子,从人类多能干细胞 (hPSCs) 有效地产生最终内皮 (DE). 这种无蛋白质的系统支持DE分化成各种细胞类型,用于治疗和药物发现.

科学领域:

干细胞生物学干细胞生物学
发育生物学是发展生物学.
生物化学生物化学

背景情况:

来自人类多能干细胞 (hPSCs) 的最终内皮 (DE) 对细胞疗法和药物发现至关重要.
目前的分化方法依赖于未定义的组件或昂贵的蛋白质,阻碍了可扩展的制造和临床应用.
在定义的,无蛋白质条件下实现均的DE分化是一个重大挑战.

研究的目的:

开发一种化学定义的,以小分子为基础的系统,用于从hPSCs中高效且具有成本效益的DE规范.
消除在DE分化中对未定义组件和重组蛋白的需求.
为了实现可扩展的DE衍生物的生产,用于治疗和研究目的.

主要方法:

小分子组合的系统优化和高通量选.
开发一个由四个组成部分 (4C) 定义的系统,用于hPSC差异化.
基因组可访问性分析以了解DE规范的机制.

主要成果:

建立了一个化学定义的,四组件 (4C) 系统,使得高效的DE规范从hPSCs没有重组蛋白质.
4C诱导的DE在体外成功分化为功能性肝细胞,肺上皮和胰腺β细胞.
德衍生物也显示出在体内差异化的潜力.
基因组分析确定了TEAD3作为一种新型关键调节剂,并揭示了4C系统的染色质重塑.

结论:

新的4C系统为DE与hPSC区分提供了一种明确,高效和具有成本效益的方法.
这一突破促进了可扩展的DE衍生物制造,用于各种应用,包括药物发现,疾病建模和细胞治疗.
这些发现为推进再生医学和制药研究提供了一个有希望的平台.

关键词:

我们的 TEAD3 团队.最终的内皮分化分化.没有增长因子的差异化系统.高通量选的高通量选

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