IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration.
Cell Stem Cell
; 30(5): 665-676.e4, 2023 05 04.
Article
en En
| MEDLINE
| ID: mdl-37146585
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina
/
Hígado
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Regeneración Hepática
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Stem Cell
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos