論文 - 詳細
| RRC ID | 67336 |
|---|---|
| 著者 | Lin HC, He Z, Ebert S, Schörnig M, Santel M, Nikolova MT, Weigert A, Hevers W, Kasri NN, Taverna E, Camp JG, Treutlein B. |
| タイトル | NGN2 induces diverse neuron types from human pluripotency. |
| ジャーナル | 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. |
| 巻・号 | 16(9) |
| ページ | 2118-2127 |
| 公開日 | 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 |
| リソース情報 | |
| ヒト・動物細胞 | 409B2(HPS0076) |