RRC ID 67336
Author Lin HC, He Z, Ebert S, Schörnig M, Santel M, Nikolova MT, Weigert A, Hevers W, Kasri NN, Taverna E, Camp JG, Treutlein B.
Title NGN2 induces diverse neuron types from human pluripotency.
Journal Stem Cell Reports
Abstract Human neurons engineered from induced pluripotent stem cells (iPSCs) through neurogenin 2 (NGN2) overexpression are widely used to study neuronal differentiation mechanisms and to model neurological diseases. However, the differentiation paths and heterogeneity of emerged neurons have not been fully explored. Here, we used single-cell transcriptomics to dissect the cell states that emerge during NGN2 overexpression across a time course from pluripotency to neuron functional maturation. We find a substantial molecular heterogeneity in the neuron types generated, with at least two populations that express genes associated with neurons of the peripheral nervous system. Neuron heterogeneity is observed across multiple iPSC clones and lines from different individuals. We find that neuron fate acquisition is sensitive to NGN2 expression level and the duration of NGN2-forced expression. Our data reveal that NGN2 dosage can regulate neuron fate acquisition, and that NGN2-iN heterogeneity can confound results that are sensitive to neuron type.
Volume 16(9)
Pages 2118-2127
Published 2021-9-14
DOI 10.1016/j.stemcr.2021.07.006
PII S2213-6711(21)00372-6
PMID 34358451
PMC PMC8452516
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / genetics* Basic Helix-Loop-Helix Transcription Factors / metabolism Cell Differentiation / genetics* Cell Line Cells, Cultured Computational Biology / methods Gene Expression Profiling Gene Expression Regulation, Developmental Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Mice Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Neurogenesis / genetics* Neurons / cytology* Neurons / metabolism* RNA-Seq Transcriptome
IF 6.032
Human and Animal Cells 409B2(HPS0076)