Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Liver transplantation (LT) is the standard therapy for individuals afflicted with end-stage liver disease. Despite notable advancements in LT technology during recent decades, the incidence of early allograft dysfunction (EAD) remains a critical concern, exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients. Unfortunately, the perplexing hepatic heterogeneity has impeded our comprehension of the cellular traits and molecular events that contribute to EAD. Herein, we constructed the pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients, with 12 liver samples from 7 donors collected at the stages of cold perfusion and portal reperfusion. By comparing 75,231 cells of non-EAD and EAD patients, we identified an EAD-associated immune niche comprising MAIT, GZMB+ GZMK+ NK cells, and S100A12+ neutrophils, which were significantly elevated in EAD patients. Moreover, we verified this immune niche and its association with EAD occurrence in two independent cohorts. Our findings clarified the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level, offering valuable insights into the EAD onset. The updated data see FigShare (https://figshare.com/articles/dataset/24521662)
Project description:Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in gene expression. We performed unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples to generate 23,980 single-nucleus transcriptomes from 3 control and 3 early diabetic nephropathy samples. All major cell types of the kidney were represented in the final dataset. Side-by-side comparison demonstrated cell-type-specific changes in gene expression that are important for ion transport, angiogenesis, and immune cell activation. In particular, we show that the diabetic thick ascending limb, late distal convoluted tubule, and principal cells all adopt a gene expression signature consistent with increased potassium secretion, including alterations in Na+/K+-ATPase, WNK1, mineralocorticoid receptor, and NEDD4L expression, as well as decreased paracellular calcium and magnesium reabsorption. We also identify strong angiogenic signatures in glomerular cell types, proximal convoluted tubule, distal convoluted tubule, and principal cells. Taken together, these results suggest that increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy.
Project description:Our data provided a genome-wide DNA methylation landscape of human early development embryos, including human MII oocytes, sperm, zygotes, 2-cell to 8-cell embryos, morula, blastocyst and postimplantation embryos at single base resolution.