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

Karow M, Camp JG, Falk S, Gerber T, Pataskar A, Gac-Santel M, Kageyama J, Brazovskaja A, Garding A, Fan W, Riedemann T, Casamassa A, Smiyakin A, Schichor C, Goetz M, Tiwari VK, Treutlein B, Berninger B (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Nature Neuroscience Nature Publishing Group

Book Volume: 21

Pages Range: 932-940

Journal Issue: 7

DOI: 10.1038/s41593-018-0168-3

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.

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Max Planck Institute for Evolutionary Anthropology / Max-Planck-Institut für evolutionäre Anthropologie DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Institut für Molekulare Biologie gGmbH / Institute of Molecular Biology (IMB) DE Germany (DE) Miltenyi Biotec GmbH DE Germany (DE)

How to cite

APA:

Karow, M., Camp, J.G., Falk, S., Gerber, T., Pataskar, A., Gac-Santel, M.,... Berninger, B. (2018). Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. Nature Neuroscience, 21(7), 932-940. https://doi.org/10.1038/s41593-018-0168-3

MLA:

Karow, Marisa, et al. "Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program." Nature Neuroscience 21.7 (2018): 932-940.

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