Project Description

Dr Helena Kilpinen

University College London, UK

Common genetic variation drives molecular heterogeneity in human iPSCs

Advances in single-cell sequencing analysis

Tuesday 4 July 2017

Helena received her PhD in 2011 from the University of Helsinki (Finland), where she studied the genetic mechanisms underlying autism spectrum disorders. Between 2011 and 2016 she worked as a postdoctoral researcher at the University of Geneva (Switzerland) and EMBL-EBI in Cambridge (UK). During this time, she studied how DNA sequence variation influences different levels of gene regulation in human cells. She joined the Human Induced Pluripotent Stem Cells Initiative ( in 2014 and has since focused on characterizing non-coding genetic variation in induced pluripotent stem cells (iPSC). Helena currently leads a research group at the Genetics and Genomic Medicine programme at the UCL Great Ormond Street Institute of Child Health in London. She is a MRC eMedLab Career Development Fellow and has an appointment also with the Cellular Genetics programme at the Wellcome Trust Sanger Institute in Cambridge. Helena’s research combines computational and experimental approaches in iPSCs and iPSC-derived cell types to comprehensively model the cellular disease mechanisms of rare human diseases in early development.
Induced pluripotent stem cells (iPSC) are increasingly used to model functional effects of human disease alleles. However, variable characterization of many existing iPSC lines limits their use for research. The Human Induced Pluripotent Stem Cells Initiative ( has generated a reference panel of high-quality iPSCs from 350 healthy individuals and 210 individuals with a rare genetic disorder in order to characterize the heterogeneity and sources of biological variability in these lines in the context of genetic changes. Rapidly accumulating data within the HipSci resource allows integrative analysis of diverse molecular and cell-level phenotypes that will advance our understanding of cellular pluripotency and provide a fundamental baseline for disease-specific studies in iPSCs.

I will present results obtained from 711 iPSC lines derived from 301 healthy individuals that were analyzed in a framework that captures variability across individuals, lines, and single cells. Specifically, we found that donor effects are the major driver of cellular heterogeneity in iPSCs, and assessed the phenotypic consequences of rare, genomic copy number mutations that are recurrently seen following iPSC reprogramming. We generated a comprehensive map of regulatory variants affecting the transcriptome of pluripotent stem cells and show that they may drive disease susceptibility through molecular changes occurring early in development, which are not captured by adult tissues. Finally, we have used iPSCs to characterize gene regulation during cellular differentiation on the level of single-cells.

Presentation slides are not available from the speaker.