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Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.

Abstract：

:Large cohorts of human induced pluripotent stem cells (iPSCs) from healthy donors are a potentially powerful tool for investigating the relationship between genetic variants and cellular behavior. Here, we integrate high content imaging of cell shape, proliferation, and other phenotypes with gene expression and DNA sequence datasets from over 100 human iPSC lines. By applying a dimensionality reduction approach, Probabilistic Estimation of Expression Residuals (PEER), we extracted factors that captured the effects of intrinsic (genetic concordance between different cell lines from the same donor) and extrinsic (cell responses to different fibronectin concentrations) conditions. We identify genes that correlate in expression with intrinsic and extrinsic PEER factors and associate outlier cell behavior with genes containing rare deleterious non-synonymous SNVs. Our study, thus, establishes a strategy for examining the genetic basis of inter-individual variability in cell behavior.

journal_name

Cell Rep

journal_title

Cell reports

authors

Vigilante A,Laddach A,Moens N,Meleckyte R,Leha A,Ghahramani A,Culley OJ,Kathuria A,Hurling C,Vickers A,Wiseman E,Tewary M,Zandstra PW,HipSci Consortium.,Durbin R,Fraternali F,Stegle O,Birney E,Luscombe NM,Danovi D,

doi

10.1016/j.celrep.2019.01.094

subject

Has Abstract

pub_date

2019-02-19 00:00:00

pages

2078-2087.e3

issue

8

issn

2211-1247

pii

S2211-1247(19)30131-7

journal_volume

26

pub_type

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