DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells.

Autor:	Roost MS; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Slieker RC; Molecular Epidemiology Section, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Bialecka M; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., van Iperen L; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Gomes Fernandes MM; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., He N; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Suchiman HED; Molecular Epidemiology Section, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Szuhai K; Department of Molecular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Carlotti F; Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands., de Koning EJP; Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.; Hubrecht Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands., Mummery CL; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Heijmans BT; Molecular Epidemiology Section, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Chuva de Sousa Lopes SM; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands. lopes@lumc.nl.; Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. lopes@lumc.nl.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2017 Oct 13; Vol. 8 (1), pp. 908. Date of Electronic Publication: 2017 Oct 13.
DOI:	10.1038/s41467-017-01077-3
Abstrakt:	Determining cell identity and maturation status of differentiated pluripotent stem cells (PSCs) requires knowledge of the transcriptional and epigenetic trajectory of organs during development. Here, we generate a transcriptional and DNA methylation atlas covering 21 organs during human fetal development. Analysis of multiple isogenic organ sets shows that organ-specific DNA methylation patterns are highly dynamic between week 9 (W9) and W22 of gestation. We investigate the impact of reprogramming on organ-specific DNA methylation by generating human induced pluripotent stem cell (hiPSC) lines from six isogenic organs. All isogenic hiPSCs acquire DNA methylation patterns comparable to existing hPSCs. However, hiPSCs derived from fetal brain retain brain-specific DNA methylation marks that seem sufficient to confer higher propensity to differentiate to neural derivatives. This systematic analysis of human fetal organs during development and associated isogenic hiPSC lines provides insights in the role of DNA methylation in lineage commitment and epigenetic reprogramming in humans.While DNA methylation and gene expression data are widely available for animal models, comprehensive data from human development is rarer. Here, the authors generated transcriptional and DNA methylation data from 21 organs during human development and 6 isogenic induced pluripotent stem cell lines.
Databáze:	MEDLINE
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