Department of Genetics, Yale University School of Medicine, New Haven, United States
David G Gonzalez
Department of Genetics, Yale University School of Medicine, New Haven, United States
Sangbum Park
Department of Genetics, Yale University School of Medicine, New Haven, United States; Institute for Quantitative Health Science & Engineering (IQ), Michigan State University, East Lansing, United States; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, United States; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, United States
Yanbo Chen
Department of Genetics, Yale University School of Medicine, New Haven, United States
Elizabeth Lathrop
Department of Genetics, Yale University School of Medicine, New Haven, United States
Biao Cai
Department of Biostatistics, Yale University School of Public Health, New Haven, United States
Tianchi Xin
Department of Genetics, Yale University School of Medicine, New Haven, United States
Hongyu Zhao
Department of Genetics, Yale University School of Medicine, New Haven, United States; Department of Biostatistics, Yale University School of Public Health, New Haven, United States
Department of Genetics, Yale University School of Medicine, New Haven, United States; Deparment of Cell Biology, Yale University School of Medicine, New Haven, United States
Department of Genetics, Yale University School of Medicine, New Haven, United States
Katie Cockburn
Department of Genetics, Yale University School of Medicine, New Haven, United States; Department of Biochemistry and Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Canada
Department of Genetics, Yale University School of Medicine, New Haven, United States; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, United States; Departments of Cell Biology and Dermatology, Yale Stem Cell Center, Yale Cancer Center, Yale University School of Medicine, New Haven, United States
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.
