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dc.creatorLin, Shengda
dc.creatorNascimento, Elisabete M.
dc.creatorGajera, Chandresh R.
dc.creatorChen, Lu
dc.creatorNeuhöfer, Patrick
dc.creatorGarbuzov, Alina
dc.creatorWang, Sui
dc.creatorArtandi, Steven E.
dc.date.accessioned2023-10-27T20:14:05Z
dc.date.available2023-10-27T20:14:05Z
dc.date.issued2018-04-04
dc.identifier.citationLin S, Nascimento EM, Gajera CR, Chen L, Neuhöfer P, Garbuzov A, et al. Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury. Nature. 2018 Apr 4;556: 244–248. doi:10.1038/s41586-018-0004-7.
dc.identifier.issn1476-4687
dc.identifier.urihttp://hdl.handle.net/20.500.12613/9098
dc.description.abstractHepatocytes are replenished gradually during homeostasis and robustly after liver injury1, 2. In adults, new hepatocytes originate from the existing hepatocyte pool3,4,5,6,7,8, but the cellular source of renewing hepatocytes remains unclear. Telomerase is expressed in many stem cell populations, and mutations in telomerase pathway genes have been linked to liver diseases9,10,11. Here we identify a subset of hepatocytes that expresses high levels of telomerase and show that this hepatocyte subset repopulates the liver during homeostasis and injury. Using lineage tracing from the telomerase reverse transcriptase (Tert) locus in mice, we demonstrate that rare hepatocytes with high telomerase expression (TERTHigh hepatocytes) are distributed throughout the liver lobule. During homeostasis, these cells regenerate hepatocytes in all lobular zones, and both self-renew and differentiate to yield expanding hepatocyte clones that eventually dominate the liver. In response to injury, the repopulating activity of TERTHigh hepatocytes is accelerated and their progeny cross zonal boundaries. RNA sequencing shows that metabolic genes are downregulated in TERTHigh hepatocytes, indicating that metabolic activity and repopulating activity may be segregated within the hepatocyte lineage. Genetic ablation of TERTHigh hepatocytes combined with chemical injury causes a marked increase in stellate cell activation and fibrosis. These results provide support for a ‘distributed model’ of hepatocyte renewal in which a subset of hepatocytes dispersed throughout the lobule clonally expands to maintain liver mass.
dc.format.extent19 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartNature, Vol. 556
dc.relation.isreferencedbyNature Research
dc.relation.isreferencedbyThis version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleDistributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury
dc.typeText
dc.type.genrePost-print
dc.contributor.groupLu Chen Lab (Temple University)
dc.contributor.groupFox Chase Cancer Center
dc.description.departmentCancer and Cellular Biology
dc.relation.doihttps://doi.org/10.1038/s41586-018-0004-7
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.creator.orcidChen|0000-0002-4571-7975
dc.temple.creatorChen, Lu
refterms.dateFOA2023-10-27T20:14:05Z


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