Back to Search
Start Over
Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program.
- Source :
-
Nature neuroscience [Nat Neurosci] 2018 Jul; Vol. 21 (7), pp. 932-940. Date of Electronic Publication: 2018 Jun 18. - Publication Year :
- 2018
-
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.
- Subjects :
- Adult
Aged
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Differentiation
Female
Gene Expression Regulation
Humans
Male
Middle Aged
Neural Stem Cells cytology
Neurons cytology
Pericytes cytology
SOXB1 Transcription Factors genetics
Young Adult
Cell Lineage physiology
Cellular Reprogramming physiology
Neural Stem Cells physiology
Neurons physiology
Pericytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1726
- Volume :
- 21
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 29915193
- Full Text :
- https://doi.org/10.1038/s41593-018-0168-3