Single-cell, single-nucleus, and spatial transcriptomics characterization of the immunological landscape in the healthy and PSC human liver.

Background & Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which there is an unmet need to understand the cellular composition of the affected liver and how it underlies disease pathogenesis. We aimed to generate a comprehensive atlas of the PSC liver using multi-omic modalities and protein-based functional validation.

Methods: We employed single-cell and single-nucleus RNA sequencing (47,156 cells and 23,000 nuclei) and spatial transcriptomics (one sample by 10x Visium and five samples with Nanostring GeoMx DSP) to profile the cellular ecosystem in 10 PSC livers.

Spatial Localization of Eubacterial 16S rRNA in Early Pregnancy Placenta and Decidua.

Bacteria derived from the maternal circulation have been suggested to seed the human placenta during pregnancy leading to development of an intrinsic placental microbiome; however, other data indicates these bacteria are artifactual contaminants. Limited research on the localization of bacteria in human placental tissue is available, which may help differentiate resident placental bacteria from contaminants. This study spatially localizes bacteria in situ in normal late first to early second trimester human placenta by 16S rRNA chromogenic in situ hybridization and demonstrates patterns consistent with both contaminants and intraparenchymal signals.

Analysis of various ATP-binding cassette transporters revealed quantification of ABCB4 as a potential diagnostic tool in primary sclerosing cholangitis (PSC).

Aims: ATP-binding cassette transporters are important proteins in regulating bile constituent transport between hepatocytes and the bile canalicular system. Dysfunctional transporters lead to accumulation of toxic bile components within hepatocytes or the biliary system, known as cholestasis, resulting in liver damage. It has been previously reported that two particular ATP-binding cassette transporters, ABCB4 and ABCB11, have altered expression in patients with primary sclerosing cholangitis (PSC).

Unraveling the Complexity of Liver Disease One Cell at a Time.

The human liver is a complex organ made up of multiple specialized cell types that carry out key physiological functions. An incomplete understanding of liver biology limits our ability to develop therapeutics to prevent chronic liver diseases, liver cancers, and death as a result of organ failure. Recently, single-cell modalities have expanded our understanding of the cellular phenotypic heterogeneity and intercellular cross-talk in liver health and disease.

Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.

The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single-cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation-related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ.