title: Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
abstract: A common metaphor for describing development is a rugged "epigenetic landscape" where cell fates are represented as attracting valleys resulting from a complex regulatory network. Here, we introduce a framework for explicitly constructing epigenetic landscapes that combines genomic data with techniques from spin-glass physics. Each cell fate is a dynamic attractor, yet cells can change fate in response to external signals. Our model suggests that partially reprogrammed cells are a natural consequence of high-dimensional landscapes, and predicts that partially reprogrammed cells should be hybrids that co-express genes from multiple cell fates. We verify this prediction by reanalyzing existing datasets. Our model reproduces known reprogramming protocols and identifies candidate transcription factors for reprogramming to novel cell fates, suggesting epigenetic landscapes are a powerful paradigm for understanding cellular identity.
authors.affiliation: Department of Physics, Boston University, Boston, Massachusetts, United States of America; Center for Regenerative Medicine, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Alex H
authors.initials: AH
authors.lastname: Lang
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, United States of America.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, United States of America; Howard Hughes Medical Institute, Boston, Massachusetts, United States of America; Center for BioDynamics, Boston University, Boston, Massachusetts, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
authors.affiliation: Department of Physics, Boston University, Boston, Massachusetts, United States of America; Center for Regenerative Medicine, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Mehta
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D013234:Stem Cells