Project description:To investigate gene expression profile of human liver MAIT cells from patients with biliary atresia, we isolated human liver MAIT cells from liver tissues of patients with biliary atresia and from adjacent non-tumor liver tissues of hepatoblastoma patients (as control) at the time of diagnosis, and subjected for bulk RNA sequencing.
Project description:We report label-free quantification of xenobiotic metabolizing enzymes (XME), transporters, redox enzymes, proteases and nucleases in 25 human liver microsomal samples, taken from patients with biliary atresia. Nearly 3500 proteins were identified and quantified. These data can be used in physiologically based pharmacokinetic models to predict appropriate drug doses drugs used in biliary atresia patients.
Project description:Liver biopsy samples were obtained from 64 infants with biliary atresia at the time of intraoperative cholangiogram. Liver biopsy samples were obtained from 14 age-matched infants with other causes of intrahepatic cholestasis, and from 7 deceased-donor children. GeneChip® Human Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was specifically regulated in the livers from patients with biliary atresia. Gene expression profiling: Liver biopsy samples obtained from infantas with other causes of intrahepatic cholestasis were served as diseased control. Liver tissue obtained from deceased-donor children were served as normal control. A molecular signataure of biliary atresia at the time of diagnosis was identified by comparing hepatic gene expression profile from biliary atresia to those from diseased and normal controls. This dataset is part of the TransQST collection.
Project description:Biliary atresia (BA) is an devastating pediatric cholangiopathy and the leading indication for liver transplant in children worldwide. An in vitro cell system for investigating BA is still lacking. We develop an in vitro cell culture system to mimic immune dysfunction of biliary atresia by coculturing human peripheral blood mononuclear cells (PBMC) with rotavirus treated or PBS treated human cholangiocyte cell line H69. Single cell RNA sequencing analysis of PBMC after coculture was applied to validate the efficacy and fidelity of cell system.
Project description:Liver biopsy samples were obtained from 64 infants with biliary atresia at the time of intraoperative cholangiogram. Liver biopsy samples were obtained from 14 age-matched infants with other causes of intrahepatic cholestasis, and from 7 deceased-donor children. GeneChip® Human Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was specifically regulated in the livers from patients with biliary atresia.
Project description:We performed single cell 5' RNA sequencing, and B cell receptor and T cell receptor V(D)J sequencing analyses on liver biopsies of nine patients with biliary atresia and three patients with choledochal cyst at diagnosis to generate the liver cell atlas.
Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.
Project description:We investigated bile-acid induced gene expression patterns in regulatory T-cells, and applied those gene sets to gene expression profiles of liver samples obtained from children with biliary atresia and intrahepatic cholestasis. Patient subgroups identified using the regulatory T-cell gene sets were then assessed for association with two-year outcome in patients with biliary atresia.
