Cell Stem Cell：新型混合剂可将成体细胞重编程为多能性干细胞

  近日，刊登在国际著名杂志Cell Stem Cell上的一篇研究论文中，来自希伯来大学的研究人员开发了一种新型的混合剂，其可以高效地诱导成体细胞转变成为高质量的多能性干细胞；再生医学是一项最新涉及多种领域的研究项目，其主要目的是通过细胞移植移除机体损伤的细胞、组织或者器官，由于基于人类胚胎的干细胞会产生一些伦理道德问题，而其也是一种可以促进成体细胞重编程为胚胎样状态细胞的一种有效途径。
  诱导多能性干细胞（iPSCs）可以被用于移除那些损伤的细胞或组织，然而科学家们发现，重编程成体细胞的过程可以引入遗传异常，从而限制细胞在研究和医学领域的有效性；为了制造iPSCs，研究者将成体细胞暴露于胚胎干细胞的活性基因混合剂中，iPSCs随后就会被诱导分化成为其它类型的细胞，比如神经细胞或肌肉细胞等；然而用于重编程细胞的标准因子则会引发高频率的遗传异常。
  这项研究中，研究者开发出了包含重编程因子新型的混合剂，其可以高效产生iPSCs，研究者Yosef Buganim博士表示，改变重编程因子会重编程成体细胞，并且产生高质量的iPSCs，利用生物信息学分析就可以设计出包含多种重编程因子的混合剂（多种重编程因子如Sall4、Lin28等）。
  这项研究揭示了重编程因子的相互作用在决定iPSCs的特性上扮演着重要角色，而且不同重编程因子的组合实际上会促进产生更高质量的iPSCs。研究者最后表示，该研究为将再生医学向临床推荐推进了一步，这样就可以帮助医生们早日实现细胞的移植疗法来治疗人类疾病，未来研究者们将对重编程的人类iPSCs进行标准化定义，从而开发其更多的潜在价值。

  PMC:
  PMID:
  The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection
  Yosef Buganim8, Styliani Markoulaki8, Niek van Wietmarschen, Heather Hoke, Tao Wu, Kibibi Ganz, Batool Akhtar-Zaidi, Yupeng He, Brian J. Abraham, David Porubsky, Elisabeth Kulenkampff, Dina A. Faddah, Linyu Shi, Qing Gao, Sovan Sarkar, Malkiel Cohen, Johanna Goldmann, Joseph R. Nery, Matthew D. Schultz, Joseph R. Ecker, Andrew Xiao, Richard A. Young, Peter M. Lansdorp, Rudolf Jaenisch
  Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A.X deposition were distinguishing features that could potentially also be applicable to human.