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相关概念视频

Forced Transdifferentiation01:28

Forced Transdifferentiation

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Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
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Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
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单细胞转录组学重建了从纤维细胞转化为心肌细胞的命运

Ziqing Liu1,2, Li Wang1,2, Joshua D Welch3

  • 1McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

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|October 27, 2017
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概括

直接血统转换可以产生新的细胞进行再生. 单细胞RNA测序显示,抑制拼接因子Ptbp1提高了纤维细胞重编程成诱导心肌细胞 (ICM) 的效率.

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科学领域:

  • 细胞生物学
  • 复原医学
  • 基因组学

背景情况:

  • 直接血统转换是组织再生和疾病建模的一个有前途的策略.
  • 由于细胞异质性和异步进展,研究纤维细胞重编程的动态过程具有挑战性.
  • 大量基因组技术不足以捕捉这些复杂的细胞转换的细微差别.

研究的目的:

  • 使用单细胞RNA测序对小鼠纤维细胞直接重新编程成诱导心肌细胞 (iCMs) 进行动态转录组变化的研究.
  • 识别不同的细胞亚群,了解重编程轨迹,并发现关键的调节因素.
  • 探索mRNA处理和拼接因素在iCM诱导的效率中的作用.

主要方法:

  • 用单细胞RNA测序 (scRNA-seq) 来分析纤维细胞重编程早期的全球转录组变化.
  • 使用无监督的缩小维度和聚类算法来识别细胞子群和重新编程路线.
  • 对候选基因,如Ptbp1进行了功能分析,包括耗尽研究,以评估它们在iCM诱导中的作用.

主要成果:

  • 在纤维细胞重编程过程中,scRNA-seq识别出了不同的分子定义子群.
  • 这项研究确定了诱导心肌细胞 (ICM) 形成的途径,以及与ICM诱导相关的细胞增殖.
  • 观察到mRNA处理和拼接因子的意外下调,Ptbp1被确定为心肌细胞特异拼接和ICM重编程的关键障碍.

结论:

  • 单细胞转录组提供了一种强大的方法来重建重编程轨迹并识别中间细胞状态.
  • Ptbp1是ICM重编程的重要障碍,其耗尽可以提高心脏基因表达和重编程的效率.
  • 该研究确定了ICM丰富的新型表面标记物,并揭示了重编程因子表达和细胞重编程进展之间的相关性.