Spatial-Temporal Lineage Restrictions of Embryonic p63+ Progenitors Establish Distinct Stem Cell Pools in Adult Airways

Yang, Ying; Riccio, Paul; Schotsaert, Michael; Mori, Munemasa; Lü, Jining; Lee, Dong-Kee; García‐Sastre, Adolfo; Xu, Jianming; Cardoso, Wellington V.

doi:10.1016/j.devcel.2018.03.001

Cited by 183 publications

(214 citation statements)

References 26 publications

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“…Hence, BASCs have to originate from more mature cells at later stages, probably from partially dedifferentiating Club or AT2 cells, which is also supported by RNA‐seq analysis of BASCs. Of course, we cannot exclude a yet unknown stem cell population, but Trp63 + basal stem cells seem unlikely candidates, since according to a recent cell tracing study, Trp63 + basal stem cells do not seem to contribute directly to alveolar epithelial cells (Yang et al , ).…”

Section: Discussionmentioning

confidence: 94%

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

et al. 2019

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Bronchioalveolar stem cells (BASCs) are a potential source for lung regeneration, but direct in vivo evidence for a multipotential lineage contribution during homeostasis and disease is critically missing, since specific genetic labeling of BASCs has not been possible. We developed a novel cell tracing approach based on intein‐mediated assembly of newly engineered split‐effectors, allowing selective targeting of dual‐marker expressing BASCs in the mouse lung. RNA sequencing of isolated BASCs demonstrates that BASCs show a distinct transcriptional profile, characterized by co‐expression of bronchiolar and alveolar epithelial genes. We found that BASCs generate the majority of distal lung airway cells after bronchiolar damage but only moderately contribute to cellular turnover under homeostatic conditions. Importantly, DTA‐mediated ablation of BASCs compromised proper regeneration of distal airways. The study defines BASCs as crucial components of the lung repair machinery and provides a paradigmatic example for the detection and manipulation of stem cells that cannot be recognized by a single marker alone.

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Section: Discussionmentioning

confidence: 94%

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

et al. 2019

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“…Several other reports also show the generation of ATII cells (Chen et al, 2017;Huang et al, 2014;Jacob et al, 2017;Yamamoto et al, 2017). Neither mature NGFR + basal cells (BCs) (Rock et al, 2009), the stem cells of the airways, nor ATI cells were ever generated however, perhaps because both cell types arise late in development (Frank et al, 2016;Yang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Glycogen Synthase Kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture

Snoeck

Carvalho

Strikoudis

et al. 2018

Preprint

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Although strategies for directed differentiation of human pluripotent stem cells (hPSCs) into lung and airway have been established, terminal maturation of the cells remains a vexing problem. We show here that in Collagen I 3D cultures in the absence of glycogen synthase kinase 3 (GSK3) inhibition, hPSC-derived lung progenitors (LPs) undergo multilineage maturation into proximal cells arranged in pseudostratified epithelia, type I alveolar epithelial cells and morphologically mature type II cells. Enhanced cell cycling, one of the signaling outputs of GSK3 inhibition, plays a role in the maturation-inhibiting effect of GSK3 inhibition. Using this model, we show NOTCH signaling induced a distal at the expense of a proximal and ciliated cell fate, while WNT signaling promoted a proximal, club cell fate, thus implicating both signaling pathways in proximodistal specification in human lung development. These findings establish an approach to achieve multilineage maturation of lung and airway cells from hPSCs, demonstrate a pivotal role of GSK3 in the maturation of lung progenitors, and provide novel insight into proximodistal specification during human lung development.

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“…Early during branching morphogenesis, when the lung epithelium is patterned into distal Sox9+ and proximal Sox2+ (airway) compartments, Yap is preferentially localized to the nucleus of distal bud tips. Lineage studies show that tip cells function as progenitors for the cell types of both the distal and proximal epithelial compartments (Rawlins, Clark, Xue, & Hogan, ; Y. Yang et al, ). Disruption of Yap in the lung epithelium of Shh Cre ; Yap f/f mice show that, although not required for specification of the distal progenitors, Yap is crucial to form the Sox2+ epithelial compartment.…”

Section: Transcriptional Roles Of Yap/tazmentioning

confidence: 99%

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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Spatial-Temporal Lineage Restrictions of Embryonic p63+ Progenitors Establish Distinct Stem Cell Pools in Adult Airways

Cited by 183 publications

References 26 publications

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo

Glycogen Synthase Kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture

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

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