来自人类多能干细胞的造血干细胞和原生细胞
Ryohichi Sugimura1,2,3,4, Deepak Kumar Jha1,2,3,4, Areum Han1,2
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|May 18, 2017
概括
研究人员从多能干细胞中产生了功能性人体造血干细胞. 鉴定出七种转录因子可以将血源性内皮转化为干细胞和前代细胞,从而实现多个血系细胞的移植.
科学领域:
- 干细胞生物学
- 血液形成
- 基因调节
背景情况:
- 多能干细胞可以通过模仿胚胎发育来分化为各种组织.
- 通过表达特定的主转录因子,可以改变细胞命运.
研究的目的:
- 从多能干细胞生成功能性人体造血干细胞 (HSC).
- 确定促进HSC发展和多系植入的关键转录因素.
主要方法:
- 人类多能干细胞以形态基因导向分化为血源性内皮.
- 对26个候选转录因子进行选,以确定HSC的能力.
- 在小鼠模型中评估多种血系构造.
主要成果:
- 确定了七种转录因子 (ERG,HOXA5,HOXA9,HOXA10,LCOR,RUNX1,SPI1).
- 这些因素将血源性内皮转化为HSC和原生细胞.
- 在初级和二级小鼠接受者中生成的细胞移植了髓状细胞,B细胞和T细胞.
结论:
- 形态差异化和转录因子转换的综合方法可以从多能干细胞中产生功能性HSC.
- 这种方法对人性化小鼠的血液病具有前景.
- 对遗传性血液疾病的潜在治疗应用.
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