日本研究人员在最新一期美国《国家科学院院刊》(PNAS)上发表论文说,在利用人体皮肤细胞培养(iPS细胞)时,很可能只有混在其中的一种特定细胞才能发育成iPS细胞,而这种细胞本身就具有万能性。
这一发现有可能颠覆京都大学教授山中伸弥提出的原有学说。
山中伸弥被称为“日本iPS细胞之父”。
2007年,他所在的研究小组利用基因技术将人体皮肤细胞改造成了类似胚胎干细胞的“万能细胞”,即iPS细胞。这种细胞可分化为人体多种组织细胞。
山中伸弥认为,只有从外部植入特殊的基因,细胞才能获得万能性。
而东北大学教授出泽真理等人本次研究发现,发育为iPS细胞的有可能是本来就存在于皮肤和骨骼中的一种干细胞,也就是去年公布的新型干细胞“Muse细胞”。
出泽真理率领的研究小组经实验发现,如果从人体皮肤的纤维母细胞中只提取“Muse细胞”,再植入山中伸弥培养iPS细胞时使用的4种基因,就能获得数量相当于传统方法30倍的iPS细胞,而如果利用人体皮肤中纤维母细胞中的其他细胞进行实验,使用同样的方法,则完全没有获得iPS细胞。
因此,研究小组认为只有“Muse细胞”这种特定的干细胞,才能够发育成iPS细胞。
原文阅读:
Proceedings of the National Academy of Sciences
Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts
Wakao, Shohei; Kitada, Masaaki; Kuroda, Yasumasa; Shigemoto, Taeko; Matsuse, Dai; Akashi, Hideo; Tanimura, Yukihiro; Tsuchiyama, Kenichiro; Kikuchi, Tomohiko; Goda, Makoto; Nakahata, Tatsutoshi;
Fujiyoshi, Yoshinori; Dezawa, Mari
The stochastic and elite models have been proposed for the mechanism of induced pluripotent stem (iPS) cell generation. Inthis study we report a system that supports the elite model. We previously identified multilineage-differentiating stress-enduring(Muse) cells in human dermal fibroblasts that are characterized by stress tolerance, expression of pluripotency markers, self-renewal,and the ability to differentiate into endodermal-, mesodermal-, and ectodermal-lineage cells from a single cell.
They canbe isolated as stage-specific embryonic antigen-3/CD105 double-positive cells.
When human fibroblasts were separated intoMuse and non-Muse cells and transduced with Oct3/4, Sox2, Klf4, and c-Myc, iPS cells were generated exclusively from Muse cells but not from non-Muse cells. Although some colonies were formed fromnon-Muse cells, they were unlike iPS cells.
Furthermore, epigenetic alterations were not seen, and some of the major pluripotencymarkers were not expressed for the entire period during iPS cell generation. These findings were confirmed further using cellstransduced with a single polycistronic virus vector encoding all four factors.
The results demonstrate that in adult humanfibroblasts a subset of preexisting adult stem cells whose properties are similar in some respects to those of iPS cells selectivelybecome iPS cells, but the remaining cells make no contribution to the generation of iPS cells. Therefore this system seemsto fit the elite model rather than the stochastic model.
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标签:细胞,PNAS,iPS