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Series GSE236424 Query DataSets for GSE236424
Status Public on Aug 01, 2023
Title Spatiotemporal hepatocyte heterogeneity impacts in vivo gene engineering [Visium Spatial Transcriptomics]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The liver is a central organ for physiology and metabolism, with hepatocytes being the main cell type responsible for most of its functions. Several previous studies investigated the cell types involved in tissue homeostasis and regeneration, however the mechanisms underlying post-natal liver growth and establishment of the mature hepatocyte phenotypes remain to be fully understood. Moreover, genetic modification of hepatocytes is emerging as a promising therapeutic approach, particularly for genetic diseases of the coagulation system and hepatic metabolism. Here, we investigate liver tissue dynamics in mice during post-natal growth and turnover in adulthood, by spatial transcriptomics, clonal analysis, and lineage tracing. We observe progressive establishment of metabolic zonation of hepatocytes and that only a fraction of hepatocytes proliferates in the newborn liver, generating most of the adult tissue. We assess the impact of these changes on both in vivo liver gene transfer and gene editing. We show that the age at treatment affects both the efficiency and lobule distribution of lentiviral vector-mediated gene transfer, and that preferential targeting of the more proliferating hepatocytes allows expansion of the genetically modified liver area. Overall, our findings provide new insights into the spatio-temporal dynamics of the liver during post-natal growth and hepatocyte heterogeneity, with broad implications for liver biology and therapeutic applications.
Overall design Spatial transcriptomics of 17 mouse livers, from newborn, juvenile or adult mice, either LV-transduced, 3 days post LV, or age-matched untransduced mice.
Contributor(s) Starinieri F, Milani M, Beretta S, Merelli I, Cantore A
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Submission date Jul 03, 2023
Last update date May 03, 2024
Contact name Stefano Beretta
Organization name San Raffaele Telethon Institute for Gene Therapy
Street address Via Olgettina, 60
City Milan
ZIP/Postal code 20132
Country Italy
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (23)
GSM7536059 LV treated newborn mouse - rep 1
GSM7536060 LV treated newborn mouse - rep 2
GSM7536061 LV treated newborn mouse - rep 3
This SubSeries is part of SuperSeries:
GSE236425 Spatiotemporal hepatocyte heterogeneity impacts in vivo gene engineering
BioProject PRJNA990790

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Supplementary file Size Download File type/resource
GSE236424_RAW.tar 581.1 Mb (http)(custom) TAR (of CSV, JPG, JSON, MTX, PNG, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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