Evidence map›Paper›PMID 23150208›Full record

ArticleHepatology (Baltimore, Md.)2013

Preexisting epithelial diversity in normal human livers: a tissue-tethered cytometric analysis in portal/periportal epithelial cells.

Kumiko Isse, Andrew Lesniak, Kedar Grama, John Maier, Susan Specht, Marcela Castillo-Rama, John Lunz, Badrinath Roysam, George Michalopoulos, Anthony J Demetris

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 46 citations in OpenAlex.

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  9. Liver regeneration: biological and pathological mechanisms and implications.Nature reviews. Gastroenterology & hepatology · 2021
    Review
  10. Article
  11. Cellular and molecular basis of liver regeneration.Seminars in cell & developmental biology · 2020
    Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Kumiko IsseDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Andrew Lesniak
Kedar Grama
John Maier
Susan Specht
Marcela Castillo-Rama
John Lunz
Badrinath Roysam
George Michalopoulos
Anthony J Demetris
University of Pittsburgh · USUniversity of Pittsburgh Medical Center · USUniversity of Houston · US

Funding

Tolerance Through Induction of Regulatory T CellsP01AI064343 · NIAID · YALE UNIVERSITY · PI ROTHSTEIN, DAVID M · 2006 to 2010
$7.0M
Interdisciplinary Training in Transplantation BiologyT32AI074490 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Angus W Thomson · 2007 to 2026
$4.2M
Liver Antigen - Presenting Cells in Hepatic Injury and TransplantationP01AI081678 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI THOMSON, ANGUS W · 2009 to 2010
$2.8M
Multi-dimensional Image Analysis Tools for Brain TissueR01EB005157 · NIBIB · UNIVERSITY OF HOUSTON · PI ROYSAM, BADRINATH · 2008 to 2010
$2.3M
Genotype and phenotype predictors in therapy response in renal cell carcinomaR01CA135509 · NCI · UNIVERSITY OF PENNSYLVANIA · PI FLAHERTY, KEITH T, LEE, WILLIAM M · 2009 to 2013
$2.3M
IMMUNE TOLERANCE NETWORK-266015416-266015416N01AI015416 · NIAID · REGENTS OF THE UNIVERSITY OF C · PI BLUESTONE, JEFFREY A · 2002 to 2006
–
NCI NIH HHS R01 CA135509NIAID NIH HHS N01 AI015416NIAID NIH HHS P01 AI064343NIAID NIH HHS P01 AI081678NIAID NIH HHS R01-AI-081678NIAID NIH HHS T32 AI074490NIBIB NIH HHS R01 EB005157NIBIB NIH HHS R01-EB-005157PHS HHS P01-A1-064343PHS HHS U01-A1-077867
6 · The paper itself

Abstract

unlabelledRoutine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the canals of Hering and/or metaplasia of preexisting mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high-resolution whole-slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes preexist in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. "Virtually digested" WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g., scatterplots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. The results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bipotential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa.

conclusionNovel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable preexistent hybrid epithelial diversity in normal human liver. This computationally enabled tissue analysis approach offers much broader potential beyond the results presented here.

Indexed as

PhenotypeBiliary TractEpithelial CellsHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 4HepatocytesHumansImage CytometryKeratin-19LiverHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 4HNF1B protein, humanHNF4A protein, humanKeratin-19

Identifiers

PMID23150208
PMCPMC3612393
OpenAlexW2151829576

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.