Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming
Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming
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DOI：
10.1126/science.1254745
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发表时间：
2014-08-15
期刊：
影响因子：
56.9
通讯作者：
Cibelli, Jose B.
中科院分区：
文献类型：
--
作者：
Gonzalez-Munoz, Elena;Arboleda-Estudillo, Yohanna;Cibelli, Jose B.
未受精的卵母细胞具有改造精子和体细胞核的内在能力。利用卵母细胞或特异性转录因子使细胞从分化状态转变为胚胎状态的发现被认为是生物医学领域的两大突破。在这里，我们表明，ASF1A，组蛋白重塑伴侣，特别是在中期II人类卵母细胞富集，是必要的人成人皮肤成纤维细胞（hADF）重新编程为未分化的诱导多能干细胞。我们还发现，在暴露于卵母细胞特异性旁分泌生长因子GDF9的hADF中，仅过表达ASF1A和OCT 4可以将hADF重编程为多能细胞。我们的报告强调了研究未受精的MII卵母细胞作为了解体细胞重编程分子途径的重要性。
Unfertilized oocytes have the intrinsic capacity to remodel sperm and the nuclei of somatic cells. The discoveries that cells can change their phenotype from differentiated to embryonic state using oocytes or specific transcription factors have been recognized as two major breakthroughs in the biomedical field. Here, we show that ASF1A, a histone-remodeling chaperone specifically enriched in the metaphase II human oocyte, is necessary for reprogramming of human adult dermal fibroblasts (hADFs) into undifferentiated induced pluripotent stem cell. We also show that overexpression of just ASF1A and OCT4 in hADFs exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells. Our Report underscores the importance of studying the unfertilized MII oocyte as a means to understand the molecular pathways governing somatic cell reprogramming.