10779/crick.11409966.v1
Alessandra Vigilante
Alessandra
Vigilante
Anna Laddach
Anna
Laddach
Nathalie Moens
Nathalie
Moens
Ruta Meleckyte
Ruta
Meleckyte
Andreas Leha
Andreas
Leha
Arsham Ghahramani
Arsham
Ghahramani
Oliver J Culley
Oliver J
Culley
Annie Kathuria
Annie
Kathuria
Chloe Hurling
Chloe
Hurling
Alice Vickers
Alice
Vickers
Erika Wiseman
Erika
Wiseman
Mukul Tewary
Mukul
Tewary
Peter W Zandstra
Peter W
Zandstra
HipSci Consortium
HipSci
Consortium
Richard Durbin
Richard
Durbin
Franca Fraternali
Franca
Fraternali
Oliver Stegle
Oliver
Stegle
Ewan Birney
Ewan
Birney
Nicholas M Luscombe
Nicholas M
Luscombe
Davide Danovi
Davide
Danovi
Fiona M Watt
Fiona M
Watt
Identifying extrinsic versus intrinsic drivers of variation in cell behavior in human iPSC lines from healthy donors
The Francis Crick Institute
2019
SNV
cell adhesion
dimensionality reduction
fibronectin
genetic variation
high content imaging
iPSC
stem cell niche
stem cells
HipSci Consortium
Luscombe FC001110
0601 Biochemistry and Cell Biology
2019-12-19 18:06:09
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Identifying_extrinsic_versus_intrinsic_drivers_of_variation_in_cell_behavior_in_human_iPSC_lines_from_healthy_donors/11409966
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.