Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury

Branden D. Tarlow, Milton J. Finegold, Markus Grompe

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Proliferating ducts, termed "oval cells," have long been thought to be bipotential, that is, produce both biliary ducts and hepatocytes during chronic liver injury. The precursor to oval cells is considered to be a facultative liver stem cell (LSC). Recent lineage tracing experiments indicated that the LSC is SRY-related HMG box transcription factor 9 postive (Sox9+) and can replace the bulk of hepatocyte mass in several settings. However, no clonal relationship between Sox9+ cells and the two epithelial liver lineages was established. We labeled Sox9+ mouse liver cells at low density with a multicolor fluorescent confetti reporter. Organoid formation validated the progenitor activity of the labeled population. Sox9+ cells were traced in multiple oval cell injury models using both histology and fluorescence-activated cell sorting. Surprisingly, only rare clones containing both hepatocytes and oval cells were found in any experiment. Quantitative analysis showed that Sox9+ cells contributed only minimally (+ ductal progenitor cells give rise to clonal oval cell proliferation and bipotential organoids, but rarely produce hepatocytes in vivo. Hepatocytes themselves are the predominant source of new parenchyma cells in prototypical mouse models of oval cell activation. (Hepatology 2014;60:278-289)

Original languageEnglish (US)
Pages (from-to)278-289
Number of pages12
JournalHepatology
Volume60
Issue number1
DOIs
StatePublished - 2014

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Liver
Wounds and Injuries
Hepatocytes
Organoids
Stem Cells
Gastroenterology
Histology
Flow Cytometry
Transcription Factors
Clone Cells
Epithelial Cells
Cell Proliferation
Population

ASJC Scopus subject areas

  • Hepatology

Cite this

Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. / Tarlow, Branden D.; Finegold, Milton J.; Grompe, Markus.

In: Hepatology, Vol. 60, No. 1, 2014, p. 278-289.

Research output: Contribution to journalArticle

Tarlow, Branden D. ; Finegold, Milton J. ; Grompe, Markus. / Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. In: Hepatology. 2014 ; Vol. 60, No. 1. pp. 278-289.
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