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

Matthias S. Roost, Roderick C. Slieker, Monika Bialecka, Liesbeth Iperen, Maria M. Gomes Fernandes, Nannan He, H. Eka D. Suchiman, Karoly Szuhai, Françoise Carlotti, Eelco J. P. Koning, Christine L. Mummery, Bastiaan T. Heijmans and Susana M. Chuva de Sousa Lopes ()
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Matthias S. Roost: Leiden University Medical Center
Roderick C. Slieker: Leiden University Medical Center
Monika Bialecka: Leiden University Medical Center
Liesbeth Iperen: Leiden University Medical Center
Maria M. Gomes Fernandes: Leiden University Medical Center
Nannan He: Leiden University Medical Center
H. Eka D. Suchiman: Leiden University Medical Center
Karoly Szuhai: Leiden University Medical Center
Françoise Carlotti: Leiden University Medical Center
Eelco J. P. Koning: Leiden University Medical Center
Christine L. Mummery: Leiden University Medical Center
Bastiaan T. Heijmans: Leiden University Medical Center
Susana M. Chuva de Sousa Lopes: Leiden University Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01077-3

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