Faculty, Staff and Student Publications

Language

English

Publication Date

5-4-2023

Journal

Cell Stem Cell

DOI

10.1016/j.stem.2023.04.007

PMID

37146585

PMCID

PMC10580294

PubMedCentral® Posted Date

5-4-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Although midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated an Igfbp2-CreER knockin strain that specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21%-41% of the lobular area. After either pericentral injury with carbon tetrachloride or periportal injury with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), IGFBP2+ cells replenished lost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentially contributed to regeneration after 70% partial hepatectomy, as well as liver growth during pregnancy. Because IGFBP2 labeling increased substantially with fasting, we used single nuclear transcriptomics to explore zonation as a function of nutrition, revealing that the zonal division of labor shifts dramatically with fasting. These studies demonstrate the contribution of IGFBP2-labeled zone 2 hepatocytes to liver homeostasis and regeneration.

Keywords

Hepatectomy, Hepatocytes, Homeostasis, Liver, Liver Regeneration, Insulin-Like Growth Factor Binding Protein 2, lineage tracing, midlobular hepatocytes, regeneration, zonation, zone 2

Published Open-Access

yes

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