Articles by Yuval Rinkevich in JoVE
Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration Jonathan M. Tsai1,2, Irving L Weissman1,2, Yuval Rinkevich3,4 1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 2Department of Developmental Biology, Stanford University School of Medicine, 3Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, 4German Center for Lung Research (DZL) Here, we present a new method for partial resection of the left hepatic lobe in neonatal (day 0) mice. This new protocol is suitable for studying acute liver injury and injury response in the neonatal setting.
Other articles by Yuval Rinkevich on PubMed
Localized Hepatic Lobular Regeneration by Central-vein-associated Lineage-restricted Progenitors Proceedings of the National Academy of Sciences of the United States of America. 04, 2017 | Pubmed ID: 28330992 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.
Two Succeeding Fibroblastic Lineages Drive Dermal Development and the Transition from Regeneration to Scarring Nature Cell Biology. Apr, 2018 | Pubmed ID: 29593327 During fetal development, mammalian back-skin undergoes a natural transition in response to injury, from scarless regeneration to skin scarring. Here, we characterize dermal morphogenesis and follow two distinct embryonic fibroblast lineages, based on their history of expression of the engrailed 1 gene. We use single-cell fate-mapping, live three dimensional confocal imaging and in silico analysis coupled with immunolabelling to reveal unanticipated structural and regional complexity and dynamics within the dermis. We show that dermal development and regeneration are driven by engrailed 1-history-naive fibroblasts, whose numbers subsequently decline. Conversely, engrailed 1-history-positive fibroblasts possess scarring abilities at this early stage and their expansion later on drives scar emergence. The transition can be reversed, locally, by transplanting engrailed 1-naive cells. Thus, fibroblastic lineage replacement couples the decline of regeneration with the emergence of scarring and creates potential clinical avenues to reduce scarring.