Reprogramming cell fates: reconciling rarity with robustness
Open Access
- 9 April 2009
- Vol. 31 (5), 546-560
- https://doi.org/10.1002/bies.200800189
Abstract
The stunning possibility of “reprogramming” differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the “ground state” character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged “epigenetic landscape” with valleys representing “preprogrammed” attractor states that emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust.Keywords
This publication has 95 references indexed in Scilit:
- The ground state of embryonic stem cell self-renewalNature, 2008
- Defining Molecular Cornerstones during Fibroblast to iPS Cell Reprogramming in MouseCell Stem Cell, 2008
- Hematopoiesis: An Evolving Paradigm for Stem Cell BiologyCell, 2008
- Sequential Expression of Pluripotency Markers during Direct Reprogramming of Mouse Somatic CellsCell Stem Cell, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Perceptions of epigeneticsNature, 2007
- The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cellsNature Genetics, 2006
- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem CellsCell, 2005
- Stochasticity in gene expression: from theories to phenotypesNature Reviews Genetics, 2005
- In vitro differentiation of embryonic stem cellsCurrent Opinion in Cell Biology, 1995