日本國立成育醫(yī)療研究中心,、東京農(nóng)業(yè)大學(xué)和美國哈佛大學(xué)研究人員組成的一個(gè)研究小組日前在利用老鼠進(jìn)行的實(shí)驗(yàn)中發(fā)現(xiàn),誘導(dǎo)多能干細(xì)胞(iPS細(xì)胞)與胚胎干細(xì)胞相比,,分化發(fā)育成全身各類細(xì)胞的能力較低,。這一研究結(jié)果已刊登在最新出版的英國《自然》雜志網(wǎng)絡(luò)版上。
iPS細(xì)胞是“初始化”后的普通體細(xì)胞,,但具有和胚胎干細(xì)胞類似的功能,,能分化生成各種組織細(xì)胞。更重要的是,,它繞開了胚胎干細(xì)胞研究一直面臨的倫理和法律等諸多障礙,,因此受到科學(xué)家的青睞。
本次研究中,,研究人員將iPS細(xì)胞和胚胎干細(xì)胞分別植入實(shí)驗(yàn)用的老鼠胚胎中,,嘗試能否使其發(fā)育成健全的身體各組織,。結(jié)果發(fā)現(xiàn),植入胚胎干細(xì)胞的胚胎發(fā)育成的全身組織一切正常,,這證明胚胎干細(xì)胞能夠發(fā)育成各類細(xì)胞,。但是,植入iPS細(xì)胞的胚胎,,則很多都在中途停止發(fā)育,。這是因?yàn)槲挥趇PS細(xì)胞第12號染色體特定領(lǐng)域內(nèi)的基因群沒有發(fā)揮作用。研究人員現(xiàn)在還沒有弄清這一基因群的具體功能,。
國立成育醫(yī)療研究中心的阿久津英憲研究員指出,,人們一直期待讓人的iPS細(xì)胞發(fā)育成神經(jīng)和心肌,然后移植到患者的患處,,實(shí)現(xiàn)再生醫(yī)療,。但人體的iPS細(xì)胞也可能存在與老鼠iPS細(xì)胞一樣的問題。他認(rèn)為,,如能讓人體iPS細(xì)胞第12號染色體特定領(lǐng)域內(nèi)的基因群發(fā)揮作用,,將會取得更理想的效果。(生物谷Bioon.com)
2010干細(xì)胞技術(shù)與應(yīng)用講座圓滿結(jié)束
Science:產(chǎn)生皮膚的干細(xì)胞源于毛囊
PNAS:脂肪組織是干細(xì)胞最佳培養(yǎng)環(huán)境
Nature Biotechnology:促進(jìn)干細(xì)胞生長并抑制分化新培養(yǎng)基
Science TM:心臟干細(xì)胞療法面臨的挑戰(zhàn)
生物谷推薦原文出處:
Nature doi:10.1038/nature09017
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells
Matthias Stadtfeld1,2,3,7, Effie Apostolou1,2,3,7, Hidenori Akutsu4, Atsushi Fukuda5, Patricia Follett1, Sridaran Natesan6, Tomohiro Kono5, Toshi Shioda2 & Konrad Hochedlinger1,2,3
Howard Hughes Medical Institute at Massachusetts General Hospital, Center for Regenerative Medicine; Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Massachusetts General Hospital Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 42 Church Street, Cambridge, Massachusetts 02138, USA
Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo 157-8535, Japan
Department of BioScience, Tokyo University of Agriculture, Tokyo 156-8502, Japan
Sanofi-Aventis, 270 Albany Street, Cambridge, Massachusetts 02139, USA
These authors contributed equally to this work.
Induced pluripotent stem cells (iPSCs) have been generated by enforced expression of defined sets of transcription factors in somatic cells. It remains controversial whether iPSCs are molecularly and functionally equivalent to blastocyst-derived embryonic stem (ES) cells. By comparing genetically identical mouse ES cells and iPSCs, we show here that their overall messenger RNA and microRNA expression patterns are indistinguishable with the exception of a few transcripts encoded within the imprinted Dlk1–Dio3 gene cluster on chromosome 12qF1, which were aberrantly silenced in most of the iPSC clones. Consistent with a developmental role of the Dlk1–Dio3 gene cluster, these iPSC clones contributed poorly to chimaeras and failed to support the development of entirely iPSC-derived animals (‘all-iPSC mice’). In contrast, iPSC clones with normal expression of the Dlk1–Dio3 cluster contributed to high-grade chimaeras and generated viable all-iPSC mice. Notably, treatment of an iPSC clone that had silenced Dlk1–Dio3 with a histone deacetylase inhibitor reactivated the locus and rescued its ability to support full-term development of all-iPSC mice. Thus, the expression state of a single imprinted gene cluster seems to distinguish most murine iPSCs from ES cells and allows for the prospective identification of iPSC clones that have the full development potential of ES cells.