title: Direct lineage reprogramming via pioneer factors; a detour through developmental gene regulatory networks.
abstract: Although many approaches have been employed to generate defined fate in vitro, the resultant cells often appear developmentally immature or incompletely specified, limiting their utility. Growing evidence suggests that current methods of direct lineage conversion may rely on the transition through a developmental intermediate. Here, I hypothesize that complete conversion between cell fates is more probable and feasible via reversion to a developmentally immature state. I posit that this is due to the role of pioneer transcription factors in engaging silent, unmarked chromatin and activating hierarchical gene regulatory networks responsible for embryonic patterning. Understanding these developmental contexts will be essential for the precise engineering of cell identity.
authors.affiliation: Departments of Developmental Biology and Genetics, Center of Regenerative Medicine, Washington University School of Medicine in St. Louis, 660 S. Euclid Avenue, Campus Box 8103, St. Louis, MO 63110, USA s.morris@wustl.edu.
authors.forename: Samantha A
authors.identifier: 0000-0001-8561-4340
authors.initials: SA
authors.lastname: Morris
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D014157:Transcription Factors
keywords: Cell fate engineering; Direct lineage reprogramming; Gene regulatory networks; Pioneer transcription factors