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RESEARCH PRODUCT
Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program
Therese RiedemannSven FalkBarbara TreutleinBarbara TreutleinJ. Gray CampTobias GerberAndrej SmiyakinMagdalena GötzChristian SchichorAngela GardingAgnieska BrazovskajaVijay K. TiwariAbhijeet PataskarWenqiang FanBenedikt BerningerMalgorzata Gac-santelMarisa KarowMarisa KarowJorge KageyamaAntonella CasamassaAntonella Casamassasubject
AdultMale0301 basic medicineSomatic cellCellular differentiationBasic Helix-Loop-Helix Transcription FactorSOXB1 Transcription FactorBiologyArticleYoung Adult03 medical and health sciences0302 clinical medicineNeural Stem CellsSOX2Basic Helix-Loop-Helix Transcription FactorsHumansCell LineageNeural Stem CellAgedPericyteNeuronsSOXB1 Transcription FactorsGeneral NeuroscienceCell DifferentiationMiddle AgedNeuronCellular ReprogrammingNeural stem cellASCL1030104 developmental biologyGene Expression RegulationFemaleEctopic expressionPericytesNeural developmentReprogrammingNeuroscience030217 neurology & neurosurgeryHumandescription
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. ISSN:1097-6256 ISSN:1546-1726
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-07-01 |