重编程致力于小鼠血细胞,诱导具有定义因子的造血干细胞
Jonah Riddell1, Roi Gazit1, Brian S Garrison1
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital, MA 02116, USA.
Cell
|April 29, 2014
概括
科学家们通过使用特定的转录因子,将已死亡的血细胞重新编程成诱导血造干细胞 (iHSCs). 这些iHSC显示出多血统潜力,并重建了血液形成,为再生医学提供了新的途径.
科学领域:
- 干细胞生物学 干细胞生物学
- 血液形成 血液形成 血液形成
- 分子生物学分子生物学
背景情况:
- 造血干细胞 (HSC) 对于终身血液生产和骨髓移植至关重要.
- 了解HSC功能是开发再生疗法的关键.
研究的目的:
- 为了确定一组定义的转录因子是否可以将已提交的血细胞重新编程成功能性的HSC.
- 探索诱导HSCs (iHSCs) 在临床应用中的潜力.
主要方法:
- 六个转录因子 (Run1t1, Hlf, Lmo2, Prdm5, Pbx1, Zfp37) 在已确定的淋巴细胞和骨髓细胞原始体中的过渡性表达.
- 使用附加因子 (Mycn,Meis1) 和多性病毒进行优化.
- 单细胞分析以评估基因表达特征和分化潜力.
主要成果:
- 重编程细胞 (iHSCs) 获得了多系移植潜力.
- iHSCs表现出克隆分化能力,并重建了干/原始体区.
- 最佳的iHSCs表现出与内源性HSCs相似的基因表达特征.
- iHSCs是可以连续移植的.
结论:
- 一个定义的转录因子集足以赋予HSC身份的血液细胞.
- 血液细胞重编程为产生可移植干细胞用于临床使用提供了一个潜在的策略.
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