Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches.
Muyoung LeeQingqing GuoMijeong KimJoonhyuk ChoiAlia SeguraAlper GencerogluLucy LeBlancNereida RamirezYu Jin JangYeejin JangBum-Kyu LeeEdward M MarcotteJonghwan KimPublished in: Genome research (2024)
Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq enables time course monitoring of transcriptome changes, and with biotinylated individual TFs, it provides a multi-omics approach to understanding the mechanisms behind TF-mediated cell fate changes. Our iTF-seq study in mouse embryonic stem cells identified multiple TFs that trigger rapid transcriptome changes indicative of differentiation within a day of induction. Moreover, cells expressing these potent TFs often show a slower cell cycle and increased cell death. Further analysis using bioChIP-seq revealed that GCM1 and OTX2 act as pioneer factors and activators by increasing gene accessibility and activating the expression of lineage specification genes during cell fate conversion. iTF-seq has utility in both mapping cell fate conversion and understanding cell fate conversion mechanisms.
Keyphrases
- cell fate
- single cell
- rna seq
- genome wide
- cell cycle
- high throughput
- cell death
- cell cycle arrest
- high resolution
- transcription factor
- cell proliferation
- dna methylation
- copy number
- randomized controlled trial
- induced apoptosis
- poor prognosis
- gene expression
- climate change
- binding protein
- oxidative stress
- endoplasmic reticulum stress
- loop mediated isothermal amplification
- dna binding