Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells

Volckaert, Thomas; Yuan, Tingting; Chao, Cho-Ming; Bell, Harold W.; Sitaula, Alina; Szimmtenings, Luisa; Agha, Elie El; Chanda, Diptiman; Majka, Susan M.; Bellusci, Savério; Thannickal, Victor J.; Fässler, Reinhard; Langhe, Stijn P. De

doi:10.1016/j.devcel.2017.09.003

Cited by 111 publications

(133 citation statements)

References 49 publications

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“…These findings support a model whereby Fgf10 from the mesenchyme under the control of ß-catenin is critical for the specification of basal cells in the developing trachea. A crosstalk between Hippo signaling and Fgf10 has been shown to regulate basal cell-fueled epithelial regeneration in the adult trachea (Volckaert et al, 2017). Here, our findings support that the ß-catenin/Fgf10/Fgfr2 axis plays an important role in basal cell specification during early tracheal development.…”

Section: Fgf10/fgfr2 Signalingsupporting

confidence: 84%

Wnt/Fgf crosstalk is required for the specification of tracheal basal progenitor cells

Hou

Sun

et al. 2018

Preprint

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Basal progenitor cells are critical for the establishment and maintenance of the tracheal epithelium. However, it remains unclear how these progenitor cells are specified during foregut development. Here, we found that ablation of the Wnt chaperon protein Gpr177 (also known as Wntless) in the epithelium causes significant reduction in the numbers of basal progenitor cells accompanied by cartilage loss in Shh-Cre;Gpr177 loxp/loxp mutants. Consistent with the association between cartilage and basal cell development, Nkx2.1 + p63 + basal cells are co-present with cartilage nodules in Shh-Cre;Ctnnb1 DM/loxp mutants which keep partial cell-cell adhesion but not the transcription regulation function of ß-catenin. More importantly, deletion of Ctnnb1 in the mesenchyme leads to the loss of basal cells and cartilage concomitant with the reduced transcript levels of Fgf10 in Dermo1-Cre;Ctnnb1 loxp/loxp mutants. Furthermore, deletion of Fgf receptor 2 (Fgfr2) in the epithelium also leads to significantly reduced numbers of basal cells, supporting the importance of the Wnt/Fgf crosstalk in early tracheal development.

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Section: Fgf10/fgfr2 Signalingsupporting

confidence: 84%

Wnt/Fgf crosstalk is required for the specification of tracheal basal progenitor cells

Hou

Sun

et al. 2018

Preprint

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“…In particular, epithelium-derived WNT ligands are emerging as key mediators activating the mesenchymal niche that in turn produces FGF10, leading to epithelial stem-cell activation and regeneration. This mechanism has been shown to be critical for activating at least two types of epithelial stem/progenitor cells in the lung: basal stem cells (Balasooriya et al, 2017;Volckaert et al, 2017) and club cells (Lee et al, 2017;Volckaert et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

A smooth muscle-like niche facilitates lung epithelial regeneration

Moiseenko

Vazquez‐Armendariz

Chu

et al. 2019

Preprint

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The mammalian lung is a highly complex organ due to its branched, tree-like structure and diverse cellular composition. Recent efforts using state-of-the-art genetic lineage tracing and single-cell transcriptomics have helped reduce this complexity and delineate the ancestry and fate of various cell subpopulations during organogenesis, homeostasis and repair after injury. However, mesenchymal cell heterogeneity and function in development and disease remain a longstanding issue in the lung field. In this study, we break down smooth muscle heterogeneity into the constituent subpopulations by combining in vivo lineage tracing, single-cell RNA sequencing and in vitro organoid cultures. We identify a repair-supportive mesenchymal cell (RSMC) population that is distinct from pre-existing airway smooth muscle cells (ASMC) and is critical for regenerating the conducting airway epithelium. Progenitors of RSMCs are intertwined with airway smooth muscle, undergo active WNT signaling, transiently acquire the expression of the smooth muscle marker ACTA2 in response to epithelial injury and are marked by PDGFRα expression. Our data simplify the cellular complexity of the peribronchiolar domain of the adult lung and represent a forward step towards unraveling the role of mesenchymal cell subpopulations in instructing epithelial behavior during repair processes.

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“…Secreted Fgf10 then activates epithelial Fgfr2 signaling, expanding basal cells. Fgfr2 signaling is crucial here since targeted deletion of Fgfr2 ablates basal cells (Balasooriya, Goschorska, Piddini, & Rawlins, ; Hou et al, ; K. S. Park et al, ; Volckaert et al, , ; Volckaert & De Langhe, ; Weidenfeld, Shu, Zhang, Millar, & Morrisey, ).…”

Section: Transcriptional Roles Of Yap/tazmentioning

confidence: 99%

“…Here, Yap is often associated with its role in induction of proliferation and survival genes, or the activation of pathways, such as Wnt, which ultimately leads to these responses through feedback loop interactions. Indeed, the role of Yap in maintenance of stemness is not necessarily a cell-autonomous process, and may entail the maintenance of a niche (Barry et al, 2013;Camargo et al, 2007;Hou et al, 2019;Konsavage & Yochum, 2013;Veltri, Lang, & Lien, 2018;Volckaert et al, 2017). Below we illustrate this paradigm in basal cells.…”

Section: Roles In the Maintenance Of Stemness And Progenitor Statusmentioning

confidence: 99%

“…Fgfr2 signaling is crucial here since targeted deletion of Fgfr2 ablates basal cells (Balasooriya, Goschorska, Piddini, & Rawlins, 2017;Hou et al, 2019;K. S. Park et al, 2004;Volckaert et al, 2011Volckaert et al, , 2017Volckaert & De Langhe, 2015;Weidenfeld, Shu, Zhang, Millar, & Morrisey, 2002).…”

Section: Roles In the Maintenance Of Stemness And Progenitor Statusmentioning

confidence: 99%

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Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Soldt

Cardoso

2019

WIREs Developmental Biology

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The Hippo pathway has emerged as a crucial integrator of signals in biological events from development to adulthood and in diseases. Although extensively studied in Drosophila and in cell cultures, major gaps of knowledge still remain on how this pathway functions in mammalian systems. The pathway consists of a growing number of components, including core kinases and adaptor proteins, which control the subcellular localization of the transcriptional co‐activators Yap and Taz through phosphorylation of serines at key sites. When localized to the nucleus, Yap/Taz interact with TEAD transcription factors to induce transcriptional programs of proliferation, stemness, and growth. In the cytoplasm, Yap/Taz interact with multiple pathways to regulate a variety of cellular functions or are targeted for degradation. The Hippo pathway receives cues from diverse intracellular and extracellular inputs, including growth factor and integrin signaling, polarity complexes, and cell–cell junctions. This review highlights the mechanisms of regulation of Yap/Taz nucleocytoplasmic shuttling and their implications for epithelial cell behavior using the lung as an intriguing example of this paradigm. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Signaling Pathways > Cell Fate Signaling Establishment of Spatial and Temporal Patterns > Cytoplasmic Localization

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Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells

Cited by 111 publications

References 49 publications

Wnt/Fgf crosstalk is required for the specification of tracheal basal progenitor cells

Wnt/Fgf crosstalk is required for the specification of tracheal basal progenitor cells

A smooth muscle-like niche facilitates lung epithelial regeneration

Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

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