Probing cell identity hierarchies by fate titration and collision during direct reprogramming.

ABSTRACT: Despite the therapeutic promise of direct reprogramming, basic principles concerning fate erasure and the mechanisms to resolve cell identity conflicts remain unclear. To tackle these fundamental questions, we established a single-cell protocol for the simultaneous analysis of multiple cell fate conversion events based on combinatorial and traceable reprogramming factor expression: Collide-seq. Collide-seq revealed the lack of a common mechanism through which fibroblast-specific gene expression loss is initiated. Moreover, we found that the transcriptome of converting cells abruptly changes when a critical level of each reprogramming factor is attained, with higher or lower levels not contributing to major changes. By simultaneously inducing multiple competing reprogramming factors, we als

SUBMITTER: Hersbach BA 

PROVIDER: S-EPMC9476893 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature