Project description:The goal of this study is to understand the effects of genetic variation on gene expression in fetal-like pancreatic progenitor cells. We generated bulk RNA-seq from 107 iPSC-derived pancreatic progenitor cells (iPSC-PPC) from iPSC lines derived from 106 individuals from the iPSCORE resource. We then conducted genome-wide expression quantitative trait loci analyses to identify genetic variants associated with gene expression and isoform usage.
Project description:The goal of this study is to characterize interactions between accessible chromatin sites within a diverse collection of human iPSCs. Here, we generated 150 bulk ATAC-seq libraries for iPSCs from the iPSCORE collection. We identified sites of open chromatin and calculated the pairwise correlation between sites to characterize functional coordination of epigenetic modifications.
Project description:Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. We made induced pluripotent stem cell (iPSC) lines from HD patients and controls. Though no obvious effects of the CAG expansion on reprogramming or subsequent neural stem cell (NSC) production were seen, HD-NSCs showed CAG expansion-associated gene expression patterns and, upon differentiation, changes in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death for both medium and longer CAG repeat expansions, with some deficits greater in cells from longer repeat HD NSCs. The HD180 lines were more vulnerable than control lines to cellular stressors and BDNF withdrawal using a range of assays across consortium laboratories. This HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics. 8 NSC samples (5 HD, 3 control), of which 3 were run as replicates (2HD, 1 control), and 5 striatal-like samples (3 HD, 2 control) Contributor: The HD iPS consortium
Project description:Musunuru, Brown, Rader, and colleagues of the NHLBI NextGen consortium use multi-ethnic population cohorts of iPSCs and differentiated hepatocyte-like cells, in combination with mouse models, to discover and validate functional DNA variants and genes at blood lipid- associated loci previously identified by genome-wide association studies.
Project description:Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. We made induced pluripotent stem cell (iPSC) lines from HD patients and controls. Though no obvious effects of the CAG expansion on reprogramming or subsequent neural stem cell (NSC) production were seen, HD-NSCs showed CAG expansion-associated gene expression patterns and, upon differentiation, changes in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death for both medium and longer CAG repeat expansions, with some deficits greater in cells from longer repeat HD NSCs. The HD180 lines were more vulnerable than control lines to cellular stressors and BDNF withdrawal using a range of assays across consortium laboratories. This HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics.
Project description:The National Institute of Health (NIH) Library of integrated network-based cellular signatures (LINCS) program is premised on generation of a publicly available data resource composed of cell-based biochemical responses or “signatures” to genetic or environmental perturbations. The NeuroLINCS center focuses on human induced pluripotent stem cells (iPSCs) derived from patients with motor neuron disease and the relevant differentiated neuronal cell cultures originating from patients and healthy controls. To establish a robust data generation process we strive to provide i) workflows for the generation of various multi-omic and functional assays for iPSC-derived motor and cortical neurons, ii) public annotated data sets and iii) relevant and targetable biological pathways of two motor neuron disorders, spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Multi-omic assays are performed on aliquots of the same biological specimen and omic data integration analyses have been performed on both iPSCs and iPSC-derived motor neuron (iMN) cultures (unpublished results) Epigenomics, transcriptomics and proteomics data were collected for iPSC cultures originating from 12 individual human iPSC lines. Although iPSCs do not manifest a neurological disease state, they may be explored for asymptomatic biological defects that could ultimately be involved in disease in the context of neuronal tissues. Here we describe the biological diversity of the proteome among 12 individual genetic backgrounds and multiple cell growth replicates of iPSCs. By first defining aspects of non-disease specific biological and technical variability, true disease specific signatures of each omic assay may be extracted with greater clarity. These experiments are part of the transition of discovery proteomics to large data sets consisting of genetically diverse specimens for whole proteome analyses. Through the NIH LINCS program, the multi-omic data sets generated by NeuroLINCS are a public resource provided in tiers of data levels to enable broad applicability throughout the scientific community. From the DIA-MS proteomic analysis of iPSCs originating from 6 cell lines of district genetic backgrounds, 39 proteins recognized iPSC or embryonic stem cell markers were reproducibly quantified with consistent expression levels across all lines analyzed. Another set of consistently quantified proteins extracted from the analyses are more diverse, with little or no known direct associations to iPSCs. Interestingly, some are associated with cancer in the literature, not surprising in that malignancies are known to transition to a less differentiated, more pluripotent biological state to enable increased cell division and metastasis. Possibly even more interesting, as it is less well studied than cancer is the appearance of iPSC proteins quantified that are associated with oocyte health and fertility. Another sub-category of iPSC quantified proteins maybe considered typical housekeeping proteins of cellular metabolism, cell division and cell structure and morphology though as a public resource to be compared with other human tissue or organ cell types many allow the level of expression or isoform specificity to be unique of iPSCs. The data quality assessments and metadata provided make these DIA-MS analyses of 6 cell lines as iPSCs a rich public resource.