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Tsai, J.M.* ; Koh, P.W.* ; Stefanska, A. ; Xing, L.* ; Walmsley, G.G.* ; Poux, N.* ; Weissman, I.L.* ; Rinkevich, Y.

Localized hepatic lobular regeneration by central-vein-associated lineage-restricted progenitors.

Proc. Natl. Acad. Sci. U.S.A. 114, 3654-3659 (2017)
Verlagsversion Forschungsdaten DOI PMC
The regeneration of organ morphology and function following tissue loss is critical to restore normal physiology, yet few cases are documented in mammalian postnatal life. Partial hepatectomy of the adult mammalian liver activates compensatory hepatocyte hypertrophy and cell division across remaining lobes, resulting in restitution of organ mass but with permanent alteration of architecture. Here, we identify a time window in early postnatal life wherein partial amputation culminates in a localized regeneration instead of global hypertrophy and proliferation. Quantifications of liver mass, enzymatic activity, and immunohistochemistry demonstrate that damaged lobes underwent multilineage regeneration, reforming a lobe often indistinguishable from undamaged ones. Clonal analysis during regeneration reveals local clonal expansions of hepatocyte stem/progenitors at injured sites that are lineage but not fate restricted. Tetrachimeric mice show clonal selection occurs during development with further selections following injury. Surviving progenitors associate mainly with central veins, in a pattern of selection different from that of normal development. These results illuminate a previously unknown program of liver regeneration after acute injury and allow for exploration of latent regenerative programs with potential applications to adult liver regeneration.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hepatocyte ; Lineage-restricted Progenitors ; Liver ; Regeneration ; Stem Cells
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 114, Heft: 14, Seiten: 3654-3659 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Begutachtungsstatus