Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming

Science  15 Aug 2014:
Vol. 345, Issue 6198, pp. 822-825
DOI: 10.1126/science.1254745

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Factor in oocyte assists reprogramming

Unfertilized eggs contain components that can dedifferentiate other cells that have gone down the path toward a specific cell fate. Gonzalez-Muñoz et al. show that the protein-folding factor ASF1A facilitates this reprogramming event and it acts at a particular phase of germ cell division termed metaphase II. ASF1A helps turn differentiated cells such as human adult dermal fibroblasts into undifferentiated pluripotent stem cells.

Science, this issue p. 822


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.

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