Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation 'Memories'

Autor: Marc Jung, David Hsu, Swetha Godatha, Elizabeth Lizhar, Xiwei Wu, Jingjing Ye, Larry A. Couture, Joshua D. Tompkins, Arthur D. Riggs, Chang yi Chen, Ziguang Lin
Rok vydání: 2016
Předmět:
Pluripotent Stem Cells
0301 basic medicine
Cellular differentiation
lcsh:Medicine
Pluripotent
Biology
Regenerative medicine
General Biochemistry
Genetics and Molecular Biology
Epigenesis
Genetic
Mesoderm
03 medical and health sciences
lncRNA
Directed differentiation
Humans
Cell Lineage
Myocytes
Cardiac
Epigenetics
Induced pluripotent stem cell
Transcription factor
Cells
Cultured
Embryonic Stem Cells
Cardiomyocytes
Genetics
lcsh:R5-920
DNA methylation
lcsh:R
Epigenetic
Cell Differentiation
Exons
General Medicine
Embryonic stem cell
Cell biology
030104 developmental biology
Differentiation
Long non-coding RNA
Methylome
Good manufacturing practice
GMP
epigenetic memory
WNT
hedgehog
transforming growth factor
ROR2
PDGFRα
demethylation
TET
TDG
HOX
TBOX
Human embryonic stem cells
lcsh:Medicine (General)
Cardiomyogenesis
Transcriptome
Research Paper
Zdroj: EBioMedicine
EBioMedicine, Vol 4, Iss C, Pp 74-85 (2016)
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2016.01.021
Popis: The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors.
Highlights • Pluripotent-derived-cardiomyocytes from scalable and defined cultures were used for transcriptome and methylome studies. • Mesoderm cell purification was conducted with ROR2 and PDGFRα surface markers removing heterogeneous cell contaminants. • Residual differentiation induced exon DNA methylation constitutes a developmental “memory” of transcription Human embryonic stem cells (hESCs) represent a theoretically unlimited cell replacement source in cardiac regenerative medicine. In this report, Tompkins et al. describe the derivation, differentiation stage-specific purification, and genome-wide analysis of cardiomyocytes derived from hESCs. Key features of the molecular programs that define human cardiac muscle cell differentiation are characterized and researchers observed that cells may harbor epigenetic DNA methylation “memories” that reflect the gene activation history of important developmental genes.
Databáze: OpenAIRE
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