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A paracrine network regulates the cross-talk between human lung stem cells and the stroma

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  • E. Josue Ruiz

    (SCI (Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge))

  • Feride Oeztuerk-Winder

    (SCI (Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge))

  • Juan-Jose Ventura

    (SCI (Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge))

Abstract

The signals that regulate stem cell self-renewal and differentiation in the lung remain elusive. Lung stem cells undergo self-renewal or lineage commitment to replenish tissue, depending on cross-talk with their environment. This environment, also known as the niche, includes mesenchymal and endothelial tissues. Here we define molecular mechanisms involved in the interaction between human lung Lgr6+ stem cells (LSCs) and fibroblasts in a functional microenvironment. We reveal a central role for p38α MAPK in establishing and maintaining such cross-talk, acting in both cell types. In LSCs, p38α induces the expression of SDF-1, which activates the stroma. p38α is essential for fibroblast activation and induction of cytokine expression, in particular TNFα. This paracrine network induces a hierarchical activation leading to the recruitment of endothelium, establishing a functional microenvironment. Disruption of this cross-talk abrogates proper LSC differentiation in vivo and may lead to lung dysfunction and disease.

Suggested Citation

  • E. Josue Ruiz & Feride Oeztuerk-Winder & Juan-Jose Ventura, 2014. "A paracrine network regulates the cross-talk between human lung stem cells and the stroma," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4175
    DOI: 10.1038/ncomms4175
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