Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.

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 wi...

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Autores principales:	Alex H Lang, Hu Li, James J Collins, Pankaj Mehta
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8a4fd51465244b7eabf47a56bd2bd5d2
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id	oai:doaj.org-article:8a4fd51465244b7eabf47a56bd2bd5d2
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spelling	oai:doaj.org-article:8a4fd51465244b7eabf47a56bd2bd5d22021-11-25T05:40:51ZEpigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.1553-734X1553-735810.1371/journal.pcbi.1003734https://doaj.org/article/8a4fd51465244b7eabf47a56bd2bd5d22014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25122086/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358A 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.Alex H LangHu LiJames J CollinsPankaj MehtaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 8, p e1003734 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Alex H Lang Hu Li James J Collins Pankaj Mehta Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
description	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.
format	article
author	Alex H Lang Hu Li James J Collins Pankaj Mehta
author_facet	Alex H Lang Hu Li James J Collins Pankaj Mehta
author_sort	Alex H Lang
title	Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
title_short	Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
title_full	Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
title_fullStr	Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
title_full_unstemmed	Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
title_sort	epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8a4fd51465244b7eabf47a56bd2bd5d2
work_keys_str_mv	AT alexhlang epigeneticlandscapesexplainpartiallyreprogrammedcellsandidentifykeyreprogramminggenes AT huli epigeneticlandscapesexplainpartiallyreprogrammedcellsandidentifykeyreprogramminggenes AT jamesjcollins epigeneticlandscapesexplainpartiallyreprogrammedcellsandidentifykeyreprogramminggenes AT pankajmehta epigeneticlandscapesexplainpartiallyreprogrammedcellsandidentifykeyreprogramminggenes
_version_	1718414527974866944

Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes.

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