Your browser doesn't support javascript.
loading
Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation.
Madrigal, Pedro; Deng, Siwei; Feng, Yuliang; Militi, Stefania; Goh, Kim Jee; Nibhani, Reshma; Grandy, Rodrigo; Osnato, Anna; Ortmann, Daniel; Brown, Stephanie; Pauklin, Siim.
Afiliación
  • Madrigal P; Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • Deng S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
  • Feng Y; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0SZ, UK.
  • Militi S; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, UK.
  • Goh KJ; Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Headington, Oxford, OX3 7LD, UK.
  • Nibhani R; Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Headington, Oxford, OX3 7LD, UK.
  • Grandy R; Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Headington, Oxford, OX3 7LD, UK.
  • Osnato A; Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • Ortmann D; The Francis Crick Institute, London, NW1 1AT, UK.
  • Brown S; Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Old Road, University of Oxford, Headington, Oxford, OX3 7LD, UK.
  • Pauklin S; Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK.
Nat Commun ; 14(1): 405, 2023 01 25.
Article en En | MEDLINE | ID: mdl-36697417
Stem cells undergo cellular division during their differentiation to produce daughter cells with a new cellular identity. However, the epigenetic events and molecular mechanisms occurring between consecutive cell divisions have been insufficiently studied due to technical limitations. Here, using the FUCCI reporter we developed a cell-cycle synchronised human pluripotent stem cell (hPSC) differentiation system for uncovering epigenome and transcriptome dynamics during the first two divisions leading to definitive endoderm. We observed that transcription of key differentiation markers occurs before cell division, while chromatin accessibility analyses revealed the early inhibition of alternative cell fates. We found that Activator protein-1 members controlled by p38/MAPK signalling are necessary for inducing endoderm while blocking cell fate shifting toward mesoderm, and that enhancers are rapidly established and decommissioned between different cell divisions. Our study has practical biomedical utility for producing hPSC-derived patient-specific cell types since p38/MAPK induction increased the differentiation efficiency of insulin-producing pancreatic beta-cells.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido