Project description:This SuperSeries is composed of the following subset Series:,GSE1049: Cell Culture A and B chips EOM,GSE1052: Cell Culture A and B chips leg
Project description:iPSCs were differentiated to human liver organoids as previously described. Human liver organoids were dispersed into single-cell suspension with trypsin (0.25%) and transferred to both channels in an dual-channel organ on chip system and cultured in hepatocyte maturation media. Media flow was regulated to 30 µL/hr for both channels. After 7 days of culture, liver chips were treated with vehicle control, or DILI-related compounds APAP, FIAU, tenofovir, or a tenofovir-inarigivir combination. scRNA sequencing was performed on intact HLOs and liver chips treated with each condition to compare HLOs pre- and post-chip and provide mechanistic DILI insight of treatments. Each sample generated between 440 and 860 million barcoded reads corresponding to an estimated 4,600 to 25,000 cells per sample
Project description:In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.
Project description:Environmental Enteric Dysfunction (EED) is a chronic inflammatory condition of the intestine characterized by villus blunting, compromised intestinal barrier function, and reduced nutrient absorption. Here, we show that key genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by organoid-derived intestinal epithelial cells from EED patients and cultured in nutrient deficient medium lacking niacinamide and tryptophan (-N/-T). Exposure of EED Intestine Chips to -N/-T deficiencies resulted in transcriptional changes similar to those seen in clinical EED patient samples including congruent changes in six of the top ten upregulated genes. Exposure of EED Intestine Chips or chips lined by healthy intestinal epithelium (healthy Intestine Chips) to -N/-T medium resulted in severe villus blunting and barrier dysfunction, as well as impairment of fatty acid uptake and amino acid transport.