title: Understanding the molecular mechanisms of reprogramming.
abstract: Despite the profound and rapid advancements in reprogramming technologies since the generation of the first induced pluripotent stem cells (iPSCs) in 2006[1], the molecular basics of the process and its implications are still not fully understood. Recent work has suggested that a subset of TFs, so called "Pioneer TFs", play an important role during the stochastic phase of iPSC reprogramming [2-6]. Pioneer TFs activities differ from conventional transcription factors in their mechanism of action. They bind directly to condensed chromatin and elicit a series of chromatin remodeling events that lead to opening of the chromatin. Chromatin decondensation by pioneer factors progressively occurs during cell division and in turn exposes specific gene promoters in the DNA to which TFs can now directly bind to promoters that are readily accessible[2, 6]. Here, we will summarize recent advancements on our understanding of the molecular mechanisms underlying reprogramming to iPSC as well as the implications that pioneer Transcription Factor activities might play during different lineage conversion processes.
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA, USA; University Hospital of Würzburg, Department of Pediatrics, 2 Josef-Schneiderstrasse, 97080 Würzburg, Germany.
authors.forename: Marie N
authors.initials: MN
authors.lastname: Krause
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA, USA; Centre for Stem Cells and Regenerative Medicine, King's College London, 28th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London, UK.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sancho-Martinez
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA, USA. Electronic address: belmonte@salk.edu.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D065150:Cellular Reprogramming; D002843:Chromatin / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D044968:Regenerative Medicine / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D014157:Transcription Factors
keywords: Dedifferentiation; Development; Lineage conversion; Pioneer transcription factors; Reprogramming; iPSCs