TY - JOUR
T1 - TGF-β signaling in stromal cells acts upstream of FGF-10 to regulate epithelial stem cell growth in the adult lung
AU - McQualter, Jonathan L.
AU - McCarty, Rosa C.
AU - Van der Velden, Joanne
AU - O'Donoghue, Robert J.J.
AU - Asselin-Labat, Marie Liesse
AU - Bozinovski, Steven
AU - Bertoncello, Ivan
N1 - Funding Information:
We thank Laura Failla and Huei Jiunn Seow (Lung Health Research Centre, Australia) for their technical assistance with cell culture studies and Real-Time PCR analysis, and Yifang Hu and Gordon Smyth (The Walter and Eliza Hall Institute, Australia) for their assistance in microarray data analysis. This study was supported by grants from the Australian Stem Cell Centre (IB and JM), the National Health and Medical Research Council (NHMRC) of Australia (IB and JM Grant No. 1009374 , RO Grant No. 1025239 ), a University of Melbourne Early Career Research Fellowship (JM), an Australian Research Council Queen Elizabeth II Fellowship (MA), and Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS .
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.scr.2013.08.007
DO - 10.1016/j.scr.2013.08.007
M3 - Article
C2 - 24029687
AN - SCOPUS:84883816017
SN - 1873-5061
VL - 11
SP - 1222
EP - 1233
JO - Stem Cell Research
JF - Stem Cell Research
IS - 3
ER -