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说明：原文来源自nature由干细胞之家新闻小组成员sun_happone翻译（转帖请注明）"; G+ [$ j* V J/ z
诱导多能干细胞从人的成纤维细胞重编程的机制仍旧没有完全搞清楚。通过中间体的过程更加复杂，这种细胞中间体未能建立一个稳定的多能性状态，这很有可能未建立一个重编程因素的理想的表达环境来完成多能性的诱导。这个中间体共表达与几个不同细胞系联系在一起的基因（如神经细胞、上皮细胞和中胚层细胞），提高了在特定环境下的可能性。成纤维细胞能被诱导分化为特定的细胞系，这很有可能类似于最近的一种说法，即成纤维细胞能转化为单个细胞类型，如神经细胞、类似巨噬细胞等，然而，这些研究检测成纤维细胞的转化建立的是小鼠模型，在人类的应用的相似过程仍是个推测。2 l8 X- _9 L2 z r
我们的初步研究表明人的真皮的成纤维细胞在多能性重编程过程中主要表达OCT4,表达细胞系的分化标记物，包括人的全血的标记物CD45,当OCT1,OCT2结合相似的DNA目标膜序为OCT4时，在淋巴的形成过程中发挥了作用。OCT4仍旧在造血过程中发挥作用，通过异位表达POU蛋白质OCT4,我们证明并且描述了直接的造血过程：人的成纤维细胞转化为多能的血液细胞系。
* O4 r2 C- J) g, {, I: F原文：Mechanisms that govern induced pluripotent stem cell (iPSC) reprogramming from human fibroblasts remain poorly understood. The process is further complicated by cellular intermediates that fail to establish a stable pluripotent state, potentially due to the inability to establish the ideal expression context of reprogramming factors to complete pluripotency induction. These intermediates co-express genes associated with several differentiated lineages (neurons, epidermis and mesoderm), raising the possibility that under unique conditions, fibroblasts could be induced to differentiate towards specified lineages. This maybe akin to recent demonstrations where fibroblasts were converted into single cell types, such as neurons, cardiomyocytes and macrophage-like cells.While these studies have examined fibroblast conversion in the murine model, a similar process remains to be extrapolated towards human applications. Our preliminary observations indicated that human dermal fibroblasts (Fibs) predominantly expressing OCT4 during the pluripotent reprogramming process express lineage differentiation markers that include the human pan-haematopoietic marker CD45. While both OCT2 (also called POU2F2) and OCT1 (also called POU2F1) bind similar DNA target motifs to OCT4 (ref. 9), and play a role in lymphoid development10–12, OCT4 is yet to be implicated in haematopoiesis. Here, by ectopic expression of the POU protein OCT4, we demonstrate and characterize direct haematopoietic fate conversion to multipotent blood progenitors from fibroblasts in the human.# w: }: U! n+ F( G9 l2 |* q& Z
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个人翻译，理解不准确的语句还望大家积极指出: A) E& i2 j' t1 t4 I
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发表于 2010-12-27 20:49
谢谢
