TGF-β signaling in stromal cells acts upstream of FGF-10 to regulate epithelial stem cell growth in the adult lung

Jonathan L. McQualter, Rosa C. McCarty, Joanne Van der Velden, Robert J.J. O'Donoghue, Marie Liesse Asselin-Labat, Steven Bozinovski, Ivan Bertoncello

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Tissue resident mesenchymal stromal cells (MSCs) contribute to tissue regeneration through various mechanisms, including the secretion of trophic factors that act directly on epithelial stem cells to promote epithelialization. However, MSCs in tissues constitute a heterogeneous population of stromal cells and different subtypes may have different functions. In this study we show that CD166neg and CD166pos lung stromal cells have different proliferative and differentiative potential. CD166neg lung stromal cells exhibit high proliferative potential with the capacity to differentiate along the lipofibroblastic and myofibroblastic lineages, whereas CD166pos lung stromal cells have limited proliferative potential and are committed to the myofibroblastic lineage. Moreover, we show that CD166pos lung stromal cells do not share the same epithelial-supportive capacity as their CD166neg counterparts, which support the growth of lung epithelial stem cell (EpiSPC) colonies in vitro. In addition, ex vivo expansion of lung stromal cells also resulted in the loss of epithelial-supportive capacity, which could be reinstated by inhibition of the TGF-β signaling pathway. We show that epithelial-supportive capacity correlated with the level of FGF-10 expression and the reactivation of several lung development-associated genes. In summary, these studies suggest that TGF-β signaling in stromal cells acts upstream of FGF-10 to regulate epithelial stem cell growth in the adult lung.

Original languageEnglish (US)
Pages (from-to)1222-1233
Number of pages12
JournalStem Cell Research
Volume11
Issue number3
DOIs
StatePublished - Nov 1 2013

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    McQualter, J. L., McCarty, R. C., Van der Velden, J., O'Donoghue, R. J. J., Asselin-Labat, M. L., Bozinovski, S., & Bertoncello, I. (2013). TGF-β signaling in stromal cells acts upstream of FGF-10 to regulate epithelial stem cell growth in the adult lung. Stem Cell Research, 11(3), 1222-1233. https://doi.org/10.1016/j.scr.2013.08.007