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Publication : IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration.

First Author  Lin YH Year  2023
Journal  Cell Stem Cell Volume  30
Issue  5 Pages  665-676.e4
PubMed ID  37146585 Mgi Jnum  J:336043
Mgi Id  MGI:7485667 Doi  10.1016/j.stem.2023.04.007
Citation  Lin YH, et al. (2023) IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration. Cell Stem Cell 30(5):665-676.e4
abstractText  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.
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