Direct pericyte-to-neuron reprogramming via unfolding of a neural stem 
cell-like program

Karow, Marisa; Camp, J. Gray; Falk, Sven; Gerber, Tobias; Pataskar, Abhijeet; Gac-Santel, Malgorzata; Kageyama, Jorge; Brazovskaja, Agnieška; Garding, Angela; Fan, Wenqiang; Riedemann, Therese; Casamassa, Antonella; Smiyakin, Andrej; Schichor, Christian; Goetz, Magdalena; Tiwari, Vijay K.; Treutlein, Barbara; Berninger, Benedikt

doi:10.1038/s41593-018-0168-3

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Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program

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Camp, J. Gray
Modern and Archaic Human Cell Biology, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Gerber, Tobias
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Gac-Santel, Malgorzata
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Kageyama, Jorge
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Brazovskaja, Agnieška
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Treutlein, Barbara
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Citation

Karow, M., Camp, J. G., Falk, S., Gerber, T., Pataskar, A., Gac-Santel, M., et al. (2018). Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. Nature Reviews Neurology, 21, 932-940. doi:10.1038/s41593-018-0168-3.

Cite as: https://hdl.handle.net/21.11116/0000-0001-D8E5-9

Abstract

Ectopic expression of defined transcription factors can force direct cell-fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory toward distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages. During this transient state, key signaling components relevant for neural induction and neural stem cell maintenance are regulated by and functionally contribute to iN reprogramming and maturation. Thus, Ascl1- and Sox2-mediated reprogramming into a broad spectrum of iN types involves the unfolding of a developmental program via neural stem cell-like intermediates.