title: Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells.
abstract: Differentiated derivatives of human pluripotent stem cells (hPSCs) are often considered immature because they resemble foetal cells more than adult, with hPSC-derived cardiomyocytes (hPSC-CMs) being no exception. Many functional features of these cardiomyocytes, such as their cell morphology, electrophysiological characteristics, sarcomere organization and contraction force, are underdeveloped compared with adult cardiomyocytes. However, relatively little is known about how their gene expression profiles compare with the human foetal heart, in part because of the paucity of data on the human foetal heart at different stages of development. Here, we collected samples of matched ventricles and atria from human foetuses during the first and second trimester of development. This presented a rare opportunity to perform gene expression analysis on the individual chambers of the heart at various stages of development, allowing us to identify not only genes involved in the formation of the heart, but also specific genes upregulated in each of the four chambers and at different stages of development. The data showed that hPSC-CMs had a gene expression profile similar to first trimester foetal heart, but after culture in conditions shown previously to induce maturation, they cluster closer to the second trimester foetal heart samples. In summary, we demonstrate how the gene expression profiles of human foetal heart samples can be used for benchmarking hPSC-CMs and also contribute to determining their equivalent stage of development.
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Cathelijne W
authors.initials: CW
authors.lastname: van den Berg
authors.affiliation: Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, Avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okawa
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chuva de Sousa Lopes
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: van Iperen
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
authors.affiliation: Pluriomics B.V., Biopartner building 3, Galileiweg 8, Leiden 2333 BD, The Netherlands.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Braam
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Leon G
authors.initials: LG
authors.lastname: Tertoolen
authors.affiliation: Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, Avenue du Swing, Belvaux L-4367, Luxembourg.
authors.forename: Antonio
authors.initials: A
authors.lastname: del Sol
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Davis
authors.affiliation: Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands c.l.mummery@lumc.nl.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D059467:Transcriptome
keywords: Gene expression profiling; Human heart development; Human pluripotent stem cells