京都大學iPS細胞研究所4月2日發(fā)表的一份公報稱，該機構研究人員發(fā)現(xiàn)數(shù)個會阻礙“誘導多功能干細胞”（iPS細胞）培育成功的基因,。這一發(fā)現(xiàn)有望更高效地培育iPS細胞,。
iPS細胞是指體細胞經(jīng)過基因“重新編排”,，回歸胚胎干細胞的狀態(tài)，從而具有類似胚胎干細胞的分化能力,。在培育iPS細胞的過程中,，需向成熟體細胞植入4種基因，使成熟細胞“返老還童”,。由于京都大學教授山中伸彌發(fā)明了這種方法,，因此它們被日本稱為“山中四因子”。不過通常iPS細胞的成功培育幾率只有約1%,。
京都大學iPS細胞研究所講師升井伸治等人為實驗鼠的神經(jīng)細胞植入“山中四因子”后,，研究了神經(jīng)細胞中特有的158個基因的功能，結果發(fā)現(xiàn)“Pax6”等6種基因妨礙iPS細胞的培育形成,。如果增強這些基因的作用,，iPS細胞的育成幾率可降至通常水平的五分之一。
研究人員認為,，上述“負面”基因的發(fā)現(xiàn)有助于科學家更高效地培育iPS細胞,。相關研究成果已刊登在美國《國家科學院院刊》網(wǎng)絡版上。（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.
