TY  - JOUR
A1  - Lee, Muyoung
A1  - Guo, Qingqing
A1  - Kim, Mijeong
A1  - Choi, Joonhyuk
A1  - Segura, Alia
A1  - Genceroglu, Alper
A1  - LeBlanc, Lucy
A1  - Ramirez, Nereida
A1  - Jang, Yu Jin
A1  - Jang, Yeejin
A1  - Lee, Bum-Kyu
A1  - Marcotte, Edward M.
A1  - Kim, Jonghwan
T1  - Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches
Y1  - 2024/03/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 484 
EP  - 497 
DO  - 10.1101/gr.277926.123 
VL  - 34 
IS  - 3 
UR  - http://genome.cshlp.org/content/34/3/484.abstract 
N2  - 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. 
ER  -