이무영 (University of Texas at Austin)

한빛사논문

조회294

University of Texas at Austin

CV File 132 kb

Genome Res., Apr 05 2024, | https://doi.org/10.1101/gr.277926.123 Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches

Muyoung Lee,^1,3 Qingqing Guo,^1,3 Mijeong Kim,^1,3 Joonhyuk Choi,¹ Alia Segura,¹Alper Genceroglu,¹ Lucy LeBlanc,¹ Nereida Ramirez,¹ Yu Jin Jang,¹ Yeejin Jang,¹Bum-Kyu Lee,² Edward M. Marcotte,¹and Jonghwan Kim ^1,*

¹Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA
²Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, New York 12144, USA
³These authors contributed equally to this work

^*Corresponding author: correspondence to Jonghwan Kim

Abstract

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.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-09)
연구진국외 연구진
분야 생명과학 > 유전자발현

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