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

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

Research output: Chapter in Book/Report/Conference proceedingChapter

11 Citations (Scopus)

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.
LanguageEnglish
Title of host publicationNature Neuroscience
PublisherNature Publishing Group
Pages1-9
Number of pages9
ISBN (Print)1546-1726 (Electronic)1097-6256 (Linking)
DOIs
Publication statusPublished - 18 Jun 2018

Publication series

NameNature Neuroscience

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Pericytes
Neural Stem Cells
Neurons
Transcription Factors
Cell Division
Neurotransmitter Agents
Maintenance
Phenotype
Gene Expression
Brain

Cite this

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. In Nature Neuroscience (pp. 1-9). (Nature Neuroscience). Nature Publishing Group. https://doi.org/10.1038/s41593-018-0168-3
Karow, Marisa ; Camp, J. Gray ; Falk, Sven ; Gerber, Tobias ; Pataskar, Abhijeet ; Gac-Santel, Malgorzata ; Kageyama, Jorge ; Brazovskaja, Agnieska ; Garding, Angela ; Fan, Wenqiang ; Riedemann, Therese ; Casamassa, Antonella ; Smiyakin, Andrej ; Schichor, Christian ; Götz, Magdalena ; Tiwari, Vijay K. ; Treutlein, Barbara ; Berninger, Benedikt. / Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. Nature Neuroscience. Nature Publishing Group, 2018. pp. 1-9 (Nature Neuroscience).
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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, Götz, M, Tiwari, VK, Treutlein, B & Berninger, B 2018, Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. in Nature Neuroscience. Nature Neuroscience, Nature Publishing Group, pp. 1-9. https://doi.org/10.1038/s41593-018-0168-3

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, Agnieska; Garding, Angela; Fan, Wenqiang; Riedemann, Therese; Casamassa, Antonella; Smiyakin, Andrej; Schichor, Christian; Götz, Magdalena; Tiwari, Vijay K.; Treutlein, Barbara; Berninger, Benedikt.

Nature Neuroscience. Nature Publishing Group, 2018. p. 1-9 (Nature Neuroscience).

Research output: Chapter in Book/Report/Conference proceedingChapter

TY - CHAP

T1 - Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program

AU - Karow, Marisa

AU - Camp, J. Gray

AU - Falk, Sven

AU - Gerber, Tobias

AU - Pataskar, Abhijeet

AU - Gac-Santel, Malgorzata

AU - Kageyama, Jorge

AU - Brazovskaja, Agnieska

AU - Garding, Angela

AU - Fan, Wenqiang

AU - Riedemann, Therese

AU - Casamassa, Antonella

AU - Smiyakin, Andrej

AU - Schichor, Christian

AU - Götz, Magdalena

AU - Tiwari, Vijay K.

AU - Treutlein, Barbara

AU - Berninger, Benedikt

PY - 2018/6/18

Y1 - 2018/6/18

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AB - 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.

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U2 - 10.1038/s41593-018-0168-3

DO - 10.1038/s41593-018-0168-3

M3 - Chapter

SN - 1546-1726 (Electronic)1097-6256 (Linking)

T3 - Nature Neuroscience

SP - 1

EP - 9

BT - Nature Neuroscience

PB - Nature Publishing Group

ER -

Karow M, Camp JG, Falk S, Gerber T, Pataskar A, Gac-Santel M et al. Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. In Nature Neuroscience. Nature Publishing Group. 2018. p. 1-9. (Nature Neuroscience). https://doi.org/10.1038/s41593-018-0168-3