英國《自然》雜志網(wǎng)站刊登的一份研究報告說,，美國研究人員不久前成功將人類皮膚細胞直接轉(zhuǎn)化為神經(jīng)細胞，這對于再生醫(yī)學等領(lǐng)域具有重要意義,。
美國斯坦福大學醫(yī)學院的馬里厄斯·韋尼希等人報告了這項成果,。該小組曾在去年撰文說，可用3個基因?qū)嶒炇蟮钠つw細胞轉(zhuǎn)化為神經(jīng)細胞,，后來又嘗試以同樣方法改造人類皮膚細胞,，不過這樣得到的細胞只是與神經(jīng)細胞相似，不具備發(fā)送電信號的功能,。經(jīng)過長期尋找,，研究人員終于發(fā)現(xiàn)，如果加入第四個基因,，可將人類皮膚細胞直接轉(zhuǎn)化為具備發(fā)送電信號功能的神經(jīng)細胞,。
本次研究的一大成功之處是直接將人類皮膚細胞轉(zhuǎn)化為神經(jīng)細胞，而此前一些細胞轉(zhuǎn)化研究需經(jīng)過“誘導多能干細胞”階段,，即先對成年體細胞進行基因“重新編排”,，使其回歸到胚胎干細胞狀態(tài)，成為具有分化成不同組織能力的“誘導多能干細胞”,，再將其慢慢培育成所需細胞,。
研究人員說,，與使用這種方法相比，直接把皮膚細胞轉(zhuǎn)化為神經(jīng)細胞在時間上更快,，轉(zhuǎn)化生成的新細胞發(fā)生病變的風險也更少,。
不過，本次研究成果也存在一些需改進之處,。一方面是轉(zhuǎn)化成功率較低,，只有2%到4%。另一方面,，轉(zhuǎn)化得到的神經(jīng)細胞使用谷氨酸鹽作為傳遞信號的化學物質(zhì),，這限制了用它們治療帕金森氏癥的前景。在帕金森氏癥患者中,，正是使用谷氨酸鹽的那些神經(jīng)細胞出了問題,。
韋尼希說，接下來將一方面努力提高細胞直接轉(zhuǎn)化的成功率,，另一方面也將嘗試培養(yǎng)不使用谷氨酸鹽的神經(jīng)細胞,，如果能獲得成功，將為再生醫(yī)學領(lǐng)域使用這些細胞治療帕金森氏癥等神經(jīng)系統(tǒng)疾病帶來希望,。 （生物谷Bioon.com）
生物谷推薦原文出處：
Nature DOI:10.1038/nature10202
Induction of human neuronal cells by defined transcription factors
Zhiping P. Pang,Nan Yang, Thomas Vierbuchen, Austin Ostermeier,Daniel R. Fuentes, Troy Q. Yang, Ami Citri, Vittorio Sebastiano, Samuele Marro, Thomas C. Südhof1, & Marius Wernig
Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells13. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6?days after transgene activation. When combined with the basic helix–loop–helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.
