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

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Updated July 24, 2025

The 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.To 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 under 17 years of age. 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 IL-1β 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, under 9 years of age) 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. Taken together, our healthy pediatric liver atlas reveals distinct age-related signatures and provides background against which to interpret pediatric liver disease data.

Sonya MacParlandUniversity of Torontos.macparland@utoronto.ca
None
Rachel Edgar1
Sonya MacParland1
1University of Toronto
None

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/febdaddd-ad3c-4f4a-820f-ade15c48545a
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Atlas

None

Analysis Portals

None

Project Label

ASingle-CellAtlasOfHumanPediatricLiverRevealsAge-R

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

2 anatomical entities

Organ Part

5 organ parts

Selected Cell Types

peripheral blood mononuclear cell

Disease Status (Specimen)

liver disorder

Disease Status (Donor)

intestinal failure–associated liver disease

Development Stage

8 development stages

Library Construction Method

3 library construction methods

Nucleic Acid Source

single cell

Paired End

false

File Format

fastq

Cell Count Estimate

Unspecified

Donor Count

15
fastq435 file(s)
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