Association of Human iPSC Gene Signatures and X Chromosome Dosage with Two Distinct Cardiac Differentiation Trajectories.
Stem Cell Reports
; 13(5): 924-938, 2019 11 12.
Article
em En
| MEDLINE
| ID: mdl-31668852
ABSTRACT
Despite the importance of understanding how variability across induced pluripotent stem cell (iPSC) lines due to non-genetic factors (clone and passage) influences their differentiation outcome, large-scale studies capable of addressing this question have not yet been conducted. Here, we differentiated 191 iPSC lines to generate iPSC-derived cardiovascular progenitor cells (iPSC-CVPCs). We observed cellular heterogeneity across the iPSC-CVPC samples due to varying fractions of two cell types cardiomyocytes (CMs) and epicardium-derived cells (EPDCs). Comparing the transcriptomes of CM-fated and EPDC-fated iPSCs, we discovered that 91 signature genes and X chromosome dosage differences are associated with these two distinct cardiac developmental trajectories. In an independent set of 39 iPSCs differentiated into CMs, we confirmed that sex and transcriptional differences affect cardiac-fate outcome. Our study provides novel insights into how iPSC transcriptional and X chromosome gene dosage differences influence their response to differentiation stimuli and, hence, cardiac cell fate.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pericárdio
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Cromossomos Humanos X
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Miócitos Cardíacos
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Células-Tronco Pluripotentes Induzidas
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Transcriptoma
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article