Lauren Kuffler

Successful growth of stem cells and embryos can be strongly affected by genetics, with deleterious variants leading to genomic instability, treatment failures or lifelong disease. Thus it is vital to examine development in genetically unique samples, capturing the full diversity of health outcomes and ensuring translatability to underserved human populations. Despite this, diversity is lacking from most studies, and new sequencing technologies lack quality control mechanisms that had become standard in the field. These are major obstacles to capturing and understanding health outcomes in both stem cell-derived therapies and heritable disorders.

My objective in the Baker Lab is to leverage genetically diverse stem cell lines to uncover drivers of developmental deficits and cell lineage specification. I propose a novel analytical method, using data collected from genetically unique cell culture lines with deeply characterized pedigrees. We will identify and define developmental effects of genetic variation and aneuploid sub-lines within our data. We will also develop quality control (QC) tools for current state-of-the-art probe-based single cell RNA sequencing platforms (scRNA-seq). We have collected colony morphology and scRNA-seq data from a panel of 144 Diversity Outbred (DO) mouse embryonic stem cell lines (mESCs) have been grown into embryoid bodies (EBs), simulating early development and produced during stem cell differentiation protocols. The DO is drawn from founder strains with known heritable disease risks, which we have also grown and sequenced as reference points.