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Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

ABSTRACT: Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency of individual lines, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts.

SUBMITTER: Cuomo ASE

PROVIDER: S-EPMC7010688 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

Cuomo Anna S E ASE Seaton Daniel D DD McCarthy Davis J DJ Martinez Iker I Bonder Marc Jan MJ Garcia-Bernardo Jose J Amatya Shradha S Madrigal Pedro P Isaacson Abigail A Buettner Florian F Knights Andrew A Natarajan Kedar Nath KN Vallier Ludovic L Marioni John C JC Chhatriwala Mariya M Stegle Oliver O

Nature communications 20200210 1

Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. ...[more]

PMID: 32041960

Dataset Information

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

Publications

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

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