京都大学iPS细胞研究所4月2日发表的一份公报称，该机构研究人员发现数个会阻碍“诱导多功能干细胞”（iPS细胞）培育成功的基因。这一发现有望更高效地培育iPS细胞。
iPS细胞是指体细胞经过基因“重新编排”，回归胚胎干细胞的状态，从而具有类似胚胎干细胞的分化能力。在培育iPS细胞的过程中，需向成熟体细胞植入4种基因，使成熟细胞“返老还童”。由于京都大学教授山中伸弥发明了这种方法，因此它们被日本称为“山中四因子”。不过通常iPS细胞的成功培育几率只有约1%。
京都大学iPS细胞研究所讲师升井伸治等人为实验鼠的神经细胞植入“山中四因子”后，研究了神经细胞中特有的158个基因的功能，结果发现“Pax6”等6种基因妨碍iPS细胞的培育形成。如果增强这些基因的作用，iPS细胞的育成几率可降至通常水平的五分之一。
研究人员认为，上述“负面”基因的发现有助于科学家更高效地培育iPS细胞。相关研究成果已刊登在美国《国家科学院院刊》网络版上。（生物谷Bioon.com）
DOI： 10.1073/pnas.1220200110
PMC:
PMID:
Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles
Takafusa Hikichia,b, Ryo Matobac, Takashi Ikedaa,b, Akira Watanabeb, Takuya Yamamotob, Satoko Yoshitakea, Miwa Tamura-Nakanoa, Takayuki Kimuraa, Masayoshi Kamond, Mari Shimuraa, Koichi Kawakamie, Akihiko Okudad,f, Hitoshi Okochia, Takafumi Inoueg,1, Atsushi Suzukih,i,1, and Shinji Masuia,b,i,2
Transcription factors (TFs) are able to regulate differentiation-related processes, including dedifferentiation and direct conversion, through the regulation of cell type-specific transcriptional profiles. However, the functional interactions between the TFs regulating different transcriptional profiles are not well understood. Here, we show that the TFs capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage cell line, we identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. This interference occurred through a maintenance mechanism of the cell type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, the TFs that interfered with dedifferentiation in hepatic-lineage cells involved TFs with known induction activity for hepatic-lineage cells. Our results suggest that dedifferentiation suppresses a cell type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types and might facilitate the identification of TFs with induction activity in efforts to understand differentiation.
