Search bioRxiv⌕ Search

Biology subjects

Ricciuto, A.

Publications and source records attributed to Ricciuto, A..

2 recordsLinked to original sources

High-resolution spatial transcriptomics of adult and pediatric human liver with Visium HD

The liver is composed of diverse cell populations that coordinate essential metabolic and immune functions. Single-cell transcriptomics has advanced characterization of liver cellular composition, but dissociation of tissue to single-cells can introduce biases through the enrichment or depletion of cell types. Spatial transcriptomics is a complementary approach to avoid inherent bias for cell populations and to add important spatial context. The Visium HD spatial transcriptomics technology from 10X Genomics enables high-resolution spatial mapping of gene expression in tissue samples with a bin width of 2{micro}m enabling quantification of transcripts at a sub-cellular resolution. We applied Visium HD to three healthy human liver donor samples, from two adult and one pediatric donor. We identified cell types by clustering 8{micro}m bins and integration with single-cell reference maps. Differential expression analyses identified spatially distinct gene expression resulting in development of a high-resolution map of the liver. This resource provides cell-level and spatially-resolved insights into the cellular and anatomical heterogeneity of the liver to serve as a resource for researchers to identify disease-specific spatial signatures and novel therapeutic targets.

genomics↗

A Single-Cell Atlas Of Human Pediatric Liver Reveals Age-Related Hepatic Gene Signatures

Background & AimsThe liver plays a critical role in metabolism and immune function, yet the contributions of its heterogeneous cell types to these processes remain unclear. While most liver studies focus on adults, pediatric liver diseases often present differently, underscoring the need for age-specific research. Approach & ResultsTo better understand cellular drivers of childhood liver diseases, we generated single-cell RNA-seq (scRNA-seq) maps of the normal pediatric liver and used this map to examine disease-related populations in biopsies from pediatric patients with Intestinal Failure-Associated Liver Disease (IFALD). The normal pediatric liver map consists of 42,660 cells from 9 donors aged 2-17 years. Compared to normal adult liver (26,372 cells; 7 donors, age 26-69) pediatric livers exhibited differences in myeloid populations. Specifically, pediatric Kupffer-like cells (MARCO+C1QA+VSIG4+) exhibited higher expression of immune activation genes, including CCL4, CCL3 and IL1B. In vitro stimulation confirmed more IL1-{beta} secreting myeloid cells in pediatric versus adult livers, supporting these findings. Using the pediatric atlas as a reference, we analyzed three IFALD biopsies (11,969 cells; 3 donors, ages 4 months-9 years) and identified increased expression of fibrosis-associated genes (e.g., LY96) in Kupffer-like cells. Additionally, mesenchymal cells in IFALD showed fibrotic gene modules resembling adult liver cells more than healthy pediatric cells. These signatures, undetectable when comparing IFALD to adult liver alone, highlighting the value of a pediatric map. ConclusionsTaken together, our healthy pediatric liver atlas reveals distinct age-related signatures and provides background against which to interpret pediatric liver disease data. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/649149v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@8d4131org.highwire.dtl.DTLVardef@1b336d2org.highwire.dtl.DTLVardef@d43ddeorg.highwire.dtl.DTLVardef@29fadf_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗