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

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

Stachys bigelovii A. Gray

Related to Fig. 1e. List of marker genes for each keratinocyte cell state (states A–E). Table S2. Related to Fig. 3f. Differentially dispersed genes for states A–E. Table S3. Related to Fig. 4a. Genes dynamically expressed (and statistically significant) along the NCA Wnt-induced cell state transition. Cluster represents the four clusters of gene expression shown in Fig. 4a. Table S4. Related to Fig. 4b-d. List of TFs identified as regulating the NCA Wnt-induced cell state transition. (XLSX 71 kb

Additional file 1: Figure S1. of Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells

Quality control of single cell RNA-seq libraries. Figure S2. Comparison of heterogeneity and expression between transition states. (PDF 694 kb

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

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