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Live imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo.
May, Dennis; Yun, Sangwon; Gonzalez, David G; Park, Sangbum; Chen, Yanbo; Lathrop, Elizabeth; Cai, Biao; Xin, Tianchi; Zhao, Hongyu; Wang, Siyuan; Gonzalez, Lauren E; Cockburn, Katie; Greco, Valentina.
Afiliación
  • May D; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Yun S; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Gonzalez DG; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Park S; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Chen Y; Institute for Quantitative Health Science & Engineering (IQ), Michigan State University, East Lansing, United States.
  • Lathrop E; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, United States.
  • Cai B; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, United States.
  • Xin T; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Zhao H; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Wang S; Department of Biostatistics, Yale University School of Public Health, New Haven, United States.
  • Gonzalez LE; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Cockburn K; Department of Genetics, Yale University School of Medicine, New Haven, United States.
  • Greco V; Department of Biostatistics, Yale University School of Public Health, New Haven, United States.
Elife ; 122023 03 07.
Article en En | MEDLINE | ID: mdl-36880644
Stem cell differentiation requires dramatic changes in gene expression and global remodeling of chromatin architecture. How and when chromatin remodels relative to the transcriptional, behavioral, and morphological changes during differentiation remain unclear, particularly in an intact tissue context. Here, we develop a quantitative pipeline which leverages fluorescently-tagged histones and longitudinal imaging to track large-scale chromatin compaction changes within individual cells in a live mouse. Applying this pipeline to epidermal stem cells, we reveal that cell-to-cell chromatin compaction heterogeneity within the stem cell compartment emerges independent of cell cycle status, and instead is reflective of differentiation status. Chromatin compaction state gradually transitions over days as differentiating cells exit the stem cell compartment. Moreover, establishing live imaging of Keratin-10 (K10) nascent RNA, which marks the onset of stem cell differentiation, we find that Keratin-10 transcription is highly dynamic and largely precedes the global chromatin compaction changes associated with differentiation. Together, these analyses reveal that stem cell differentiation involves dynamic transcriptional states and gradual chromatin rearrangement.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Queratina-10 Límite: Animals Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Queratina-10 Límite: Animals Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido