Developmental Pathways and Specification of Intrapulmonary Stem Cells

Borok, Zea; Li, Changgong; Liebler, Janice M.; Aghamohammadi, Neema; Londhe, Vedang A.; Minoo, Parviz

doi:10.1203/01.pdr.0000203563.37626.77

Cited by 18 publications

(10 citation statements)

References 101 publications

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“…Different from other tissue stem cells, only rare BASCs may be activated to participate in epithelial repair after depletion of so-called ''transit-amplifying cells,'' cells characterized as progenies of tissue stem cells with proliferative capacity (69,165,167). Recently, the involvement of WNT signaling in lung stem cell maintenance and activation has been pointed out (168)(169)(170). Zhang and colleagues (168) demonstrated that the transcription factor, GATA6, influences the temporal appearance and number of BASC in the lung by regulating WNT signaling.…”

Section: The Wnt Signaling Pathway-stem Cell Maintenancementioning

confidence: 99%

WNT Signaling in Lung Disease

Königshoff

Eickelberg²

2010

Am J Respir Cell Mol Biol

238

107

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The WNT family of signaling proteins is essential to organ development in general and lung morphogenesis in particular. Originally identified as a developmentally active signaling pathway, the WNT pathway has recently been linked to the pathogenesis of important lung diseases, in particular lung cancer and pulmonary fibrosis. This review summarizes our current understanding about WNT signaling in lung development and disease, and is structured into three chapters. The first chapter presents an introduction to WNT signaling, outlining WNT proteins, their receptors and signaling intermediates, as well as the regulation of this complex pathway. The second chapter focuses on the role of WNT signaling in the normal embryonic and adult lung, and highlights recent findings of altered WNT signaling in lung diseases, such as lung cancer, pulmonary fibrosis, or pulmonary arterial hypertension. In the last chapter, we will discuss novel data and ideas about the biological effects of WNT signaling on the cellular level, highlighting pleiotropic effects induced by WNT ligands on distinct cell types, and how these cellular effects may be relevant to the pathogenesis of the aforementioned diseases.

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Section: The Wnt Signaling Pathway-stem Cell Maintenancementioning

confidence: 99%

WNT Signaling in Lung Disease

Königshoff

Eickelberg²

2010

Am J Respir Cell Mol Biol

238

107

View full text Add to dashboard Cite

show abstract

“…Regardless, stem cells play an essential role in the development and maturity of many organ systems including the central nervous, respiratory, cardiovascular, haematologic, immunologic and endocrine systems long before birth [97][98][99][100][101][102]. The aetiology of many diseases of the newborn is related to delayed development and immaturity.…”

Section: Nature's First Stem Cell Transplant Occurs At Birth When Thementioning

confidence: 99%

Mankind’s first natural stem cell transplant

Tolosa

Park

Eve

et al. 2010

J Cellular Molecular Medi

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The timing of the umbilical cord clamping at birth is still controversial. In the modern era of medicine, the cord has been clamped early to facilitate resuscitation and stabilization of infants. However, recently delayed cord clamping has been supported by physicians because it allows for the physiological transfer of blood from the placenta to the infant. Many clinical studies have revealed that the delayed cord clamping elevates blood volume and haemoglobin and prevents anaemia in infants. Moreover, since it was known that umbilical cord blood contains various valuable stem cells such as haematopoietic stem cells, endothelial cell precursors, mesenchymal progenitors and multipotent/pluripotent lineage stem cells, the merit of delayed cord clamping has been magnified. In this review, we discuss the advantages and disadvantages of delayed cord clamping at birth. We highlight the importance of delayed cord clamping in realizing mankind’s first stem cell transfer and propose that it should be encouraged in normal births.

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“…Activation of fibroblasts in response to injury mediates the reparative response of the epithelium (3,(7)(8)(9)(10)(11), and the roles of fibroblasts in compensatory lung growth, realveolarization following partial pneumonectomy (PNX) has been noted in several species (12)(13)(14)(15)(16)(17)(18). The availability of transgenic mice nowadays provides the tools for extensive characterization of the cellular and molecular mechanisms responsible for compensatory lung regrowth after PNX.…”

Section: Introductionmentioning

confidence: 99%

Diversity of Interstitial Lung Fibroblasts Is Regulated by Platelet-Derived Growth Factor Receptor α Kinase Activity

Green

Endale

Auer³

et al. 2016

Am J Respir Cell Mol Biol

116

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Epithelial-mesenchymal cell interactions and factors that control normal lung development are key players in lung injury, repair, and fibrosis. A number of studies have investigated the roles and sources of epithelial progenitors during lung regeneration; such information, however, is limited in lung fibroblasts. Thus, understanding the origin, phenotype, and roles of fibroblast progenitors in lung development, repair, and regeneration helps address these limitations. Using a combination of platelet-derived growth factor receptor α-green fluorescent protein (PDGFRα-GFP) reporter mice, microarray, real-time polymerase chain reaction, flow cytometry, and immunofluorescence, we characterized two distinct interstitial resident fibroblasts, myo- and matrix fibroblasts, and identified a role for PDGFRα kinase activity in regulating their activation during lung regeneration. Transcriptional profiling of the two populations revealed a myo- and matrix fibroblast gene signature. Differences in proliferation, smooth muscle actin induction, and lipid content in the two subpopulations of PDGFRα-expressing fibroblasts during alveolar regeneration were observed. Although CD140α(+)CD29(+) cells behaved as myofibroblasts, CD140α(+)CD34(+) appeared as matrix and/or lipofibroblasts. Gain or loss of PDGFRα kinase activity using the inhibitor nilotinib and a dominant-active PDGFRα-D842V mutation revealed that PDGFRα was important for matrix fibroblast differentiation. We demonstrated that PDGFRα signaling promotes alveolar septation by regulating fibroblast activation and matrix fibroblast differentiation, whereas myofibroblast differentiation was largely PDGFRα independent. These studies provide evidence for the phenotypic and functional diversity as well as the extent of specificity of interstitial resident fibroblasts differentiation during regeneration after partial pneumonectomy.

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Developmental Pathways and Specification of Intrapulmonary Stem Cells

Cited by 18 publications

References 101 publications

WNT Signaling in Lung Disease

WNT Signaling in Lung Disease

Mankind’s first natural stem cell transplant

Diversity of Interstitial Lung Fibroblasts Is Regulated by Platelet-Derived Growth Factor Receptor α Kinase Activity

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