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Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches.
Lee, Muyoung; Guo, Qingqing; Kim, Mijeong; Choi, Joonhyuk; Segura, Alia; Genceroglu, Alper; LeBlanc, Lucy; Ramirez, Nereida; Jang, Yu Jin; Jang, Yeejin; Lee, Bum-Kyu; Marcotte, Edward M; Kim, Jonghwan.
Afiliación
  • Lee M; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Guo Q; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Kim M; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Choi J; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Segura A; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Genceroglu A; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • LeBlanc L; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Ramirez N; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Jang YJ; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Jang Y; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Lee BK; Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, New York 12144, USA.
  • Marcotte EM; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
  • Kim J; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA; jonghwankim@mail.utexas.edu.
Genome Res ; 34(3): 484-497, 2024 04 25.
Article en En | MEDLINE | ID: mdl-38580401
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Diferenciación Celular Límite: Animals Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Diferenciación Celular Límite: Animals Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos