Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq.

ABSTRACT: Direct lineage reprogramming represents a remarkable conversion of cellular and transcriptome states. However, the intermediate stages through which individual cells progress during reprogramming are largely undefined. Here we use single-cell RNA sequencing at multiple time points to dissect direct reprogramming from mouse embryonic fibroblasts to induced neuronal cells. By deconstructing heterogeneity at each time point and ordering cells by transcriptome similarity, we find that the molecular reprogramming path is remarkably continuous. Overexpression of the proneural pioneer factor Ascl1 results in a well-defined initialization, causing cells to exit the cell cycle and re-focus gene expression through distinct neural transcription factors. The initial transcriptional response is relativ

SUBMITTER: Treutlein B 

PROVIDER: S-EPMC4928860 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature