Resolution of Reprogramming Transition States by Single Cell RNA-Sequencing

Guo, L.; Wang, X.; Gao, M.; Lin, L.; Kuang, J.; Mai, Y.; Wu, F.; Liu, H.; Yang, J.; Chu, S.; Song, H.; Liu, Y.; Liu, J.; Wang, J.; Pan, G.; Hutchins, A. P.; Chen, J.; Pei, D.

doi:10.1101/182535

bioRxiv · 10.1101/182535

Resolution of Reprogramming Transition States by Single Cell RNA-Sequencing

Guo, L.·Wang, X.·Gao, M.·Lin, L.·Kuang, J.·Mai, Y.·Wu, F.·Liu, H.·Yang, J.·Chu, S.·Song, H.·Liu, Y.·Liu, J.·Wang, J.·Pan, G.·Hutchins, A. P.·Chen, J.·Pei, D.

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Abstract

The Yamanaka factors convert mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through a highly heterogeneous process. Here we profile single cells undergoing an optimized 7-day reprogramming process and show that cells start reprogramming relatively in sync, but diverge into two branches around day 2. The first branch of cells expressing Cd34/Fxyd5/Psca become nonpluripotent. The second one contains cells that are first Oct4+, then Dppa5a+ and pluripotent. We show that IFN-{gamma} blocks this late transition. Our results reveal the heterogeneous nature of somatic cell reprogramming, identify Dppa5a as a marker for pluripotent and innate immunity as a potential barrier for reprogramming.\n\nOne Sentence SummarySingle cell RNA sequencing reveals a continuum of cell fates from somatic to pluripotent and Dppa5a as a marker for chimera-competent iPSCs.

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Guo, L., Wang, X., Gao, M., Lin, L., Kuang, J., Mai, Y., Wu, F., Liu, H., Yang, J., Chu, S., Song, H., Liu, Y., Liu, J., Wang, J., Pan, G., Hutchins, A. P., Chen, J., Pei, D.. 2017-08-30. Resolution of Reprogramming Transition States by Single Cell RNA-Sequencing. https://doi.org/10.1101/182535

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