scholarly journals Dynamics of the Epigenomic State of Alveolar Epithelial Progenitors Cells During Differentiation into Alveolar Type 1 and Type 2 Cells

2020 ◽  
Author(s):  
W. Zacharias ◽  
P. Kannan ◽  
A. Toth ◽  
D.T. Swarr
Keyword(s):  
Alveolar Type ◽  
Alveolar Epithelial

scholarly journals The Promise of Lung Organoids for Growth and Investigation of Pneumocystis Species

2021 ◽  
Vol 2 ◽  
Author(s):  
Nikeya Tisdale-Macioce ◽  
Jenna Green ◽  
Anne-Karina T. Perl ◽  
Alan Ashbaugh ◽  
Nathan P. Wiederhold ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Culture System ◽  
Ex Vivo ◽  
Alveolar Type ◽  
Proof Of Concept ◽  
3 Dimensional ◽  
Alveolar Epithelial

Pneumocystis species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause a lethal pneumonia. The emergence of this pneumonia in non-HIV infected persons caused by Pneumocystis jirovecii (PjP), illustrates the continued importance of and the need to understand its associated pathologies and to develop new therapies and preventative strategies. In the proposed life cycle, Pneumocystis spp. attach to alveolar type 1 epithelial cells (AEC1) and prevent gas exchange. This process among other mechanisms of Pneumocystis spp. pathogenesis is challenging to observe in real time due to the absence of a continuous ex vivo or in vitro culture system. The study presented here provides a proof-of-concept for the development of murine lung organoids that mimic the lung alveolar sacs expressing alveolar epithelial type 1 cells (AEC1) and alveolar type 2 epithelial cells (AEC2). Use of these 3-dimensional organoids should facilitate studies of a multitude of unanswered questions and serve as an improved means to screen new anti- PjP agents.

GATA6 regulates differentiation of distal lung epithelium

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2233-2246 ◽  
Author(s):  
Honghua Yang ◽  
Min Min Lu ◽  
Lili Zhang ◽  
Jeffrey A. Whitsett ◽  
Edward E. Morrisey
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Surfactant Protein ◽  
Gata Factor ◽  
Lung Epithelium ◽  
Alveolar Epithelial ◽  
Distal Lung ◽  
Transgenic Embryos

GATA6 is a member of the GATA family of zinc-finger transcriptional regulators and is the only known GATA factor expressed in the distal epithelium of the lung during development. To define the role that GATA6 plays during lung epithelial cell development, we expressed a GATA6-Engrailed dominant-negative fusion protein in the distal lung epithelium of transgenic mice. Transgenic embryos lacked detectable alveolar epithelial type 1 cells in the distal airway epithelium. These embryos also exhibited increased Foxp2 gene expression, suggesting a disruption in late alveolar epithelial differentiation. Alveolar epithelial type 2 cells, which are progenitors of alveolar epithelial type 1 cells, were correctly specified as shown by normal thyroid transcription factor 1 and surfactant protein A gene expression. However, attenuated endogenous surfactant protein C expression indicated that alveolar epithelial type 2 cell differentiation was perturbed in transgenic embryos. The number of proximal airway tubules is also reduced in these embryos, suggesting a role for GATA6 in regulating distal-proximal airway development. Finally, a functional role for GATA factor function in alveolar epithelial type 1 cell gene regulation is supported by the ability of GATA6 to trans-activate the mouse aquaporin-5 promoter. Together, these data implicate GATA6 as an important regulator of distal epithelial cell differentiation and proximal airway development in the mouse.

Transformation of alveolar Type 2 cells to Type 1 cells following exposure to NO2

1975 ◽  
Vol 22 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Michael J. Evans ◽  
Linda J. Cabral ◽  
Robert J. Stephens ◽  
Gustave Freeman
Keyword(s):  
Alveolar Type

scholarly journals Fibrinolytic niche is requested for alveolar type 2 cell-mediated alveologenesis and injury repair

2020 ◽  
Author(s):  
Ali Gibran ◽  
Runzhen Zhao ◽  
Mo Zhang ◽  
Krishan G. Jain ◽  
Jianjun Chang ◽  
...  
Keyword(s):  
Alveolar Epithelium ◽  
Influenza Viruses ◽  
Alveolar Type ◽  
Differential Rate ◽  
Alveolar Epithelial ◽  
Proliferation And Differentiation ◽  
Marked Suppression

ABSTRACTCOVID-19, SARS, and MERS are featured by fibrinolytic dysfunction. To test the role of the fibrinolytic niche in the regeneration of alveolar epithelium, we compared the self-renewing capacity of alveolar epithelial type 2 (AT2) cells and its differentiation to AT1 cells between wild type (wt) and fibrinolytic niche deficient mice (Plau−/− and Serpine1Tg). A significant reduction in both proliferation and differentiation of deficient AT2 cells was observed in vivo and in 3D organoid cultures. This decrease was mainly restored by uPA derived A6 peptide, a binding fragment to CD44 receptors. The proliferative and differential rate of CD44+ AT2 cells was greater than that of CD44− controls. There was a reduction in transepithelial ion transport in deficient monolayers compared to wt cells. Moreover, we found a marked suppression in total AT2 cells and CD44+ subpopulation in lungs from brain dead patients with acute respiratory distress syndrome (ARDS) and a mouse model infected by influenza viruses. Thus, we demonstrate that the fibrinolytic niche can regulate AT2-mediated homeostasis and regeneration via a novel uPA-A6-CD44+-ENaC cascade.

scholarly journals H 2 0 2 regulates lung ENaC via ubiquitin‐like protein Nedd8 in alveolar type 1 and type 2 cells.

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Nicholle M. Johnson ◽  
Charles A. Downs ◽  
Lisa H. Kreiner ◽  
My N. Helms
Keyword(s):  
Alveolar Type

scholarly journals Alterations in alveolar basement membranes during postnatal lung growth.

1982 ◽  
Vol 95 (2) ◽  
pp. 394-402 ◽  
Author(s):  
J S Brody ◽  
C A Vaccaro ◽  
P J Gill ◽  
J E Silbert
Keyword(s):  
Heparan Sulfate ◽  
Ruthenium Red ◽  
Basement Membranes ◽  
Alveolar Type ◽  
Age Related ◽  
Enzyme Degradation ◽  
Alveolar Formation

We studied the ultrastructural characteristics of alveolar basement membranes (ABM) and capillary basement membranes (CBM) in rat lungs at birth, at 8-10 d of age, during alveolar formation, and at 6-10 wk of age, after most alveoli have formed. We also measured in vitro lung proteoglycan and heparan sulfate synthesis at each age. We noted three major age-related changes in pulmonary basement membranes. (a) Discontinuities in the ABM through which basilar cytoplasmic foot processes extend are present beneath alveolar type-2 cells but not alveolar type-1 cells. These discontinuities are most prevalent at birth but also exist in the adult. (b) Discontinuities are also present in CBM at the two earliest time points but are maximal at 8 d of age rather than at birth. Fusions between ABM and CBM are often absent at 8 d of age, but CBM and CBM/ABM fusions were complete in the adult. (c) Heparan sulfate proteoglycans identified with ruthenium red and selective enzyme degradation are distributed equally on epithelial and interstitial sides of the ABM lamina densa at birth, but decrease on the interstitial side with age. In vitro proteoglycan and heparan sulfate accumulation at birth was two times that at 8 d and five times that in the adult. Discontinuities in ABM allow epithelial-mesenchymal interactions that may influence type-2 cells cytodifferentiation. Discontinuities in CBM suggest that capillary proliferation and neovascularization are associated with alveolar formation at 8 d. When CBM becomes complete and forms junctions with ABM, lung neovascularization likely ends as does the ability to form new alveoli.

scholarly journals Wnt signaling regulates trans-differentiation of stem cell like type 2 alveolar epithelial cells to type 1 epithelial cells

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Elhusseiny Mohamed Mahmud Abdelwahab ◽  
Judit Rapp ◽  
Diana Feller ◽  
Veronika Csongei ◽  
Szilard Pal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Wnt Signaling ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

scholarly journals Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis

2021 ◽  
Vol 118 (20) ◽  
pp. e2101100118
Author(s):  
Satoshi Watanabe ◽  
Nikolay S. Markov ◽  
Ziyan Lu ◽  
Raul Piseaux Aillon ◽  
Saul Soberanes ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Alveolar Epithelium ◽  
Protein Translation ◽  
Alveolar Type ◽  
Fatal Disease ◽  
Epithelial Repair ◽  
Old Mice

Pulmonary fibrosis is a relentlessly progressive and often fatal disease with a paucity of available therapies. Genetic evidence implicates disordered epithelial repair, which is normally achieved by the differentiation of small cuboidal alveolar type 2 (AT2) cells into large, flattened alveolar type 1 (AT1) cells as an initiating event in pulmonary fibrosis pathogenesis. Using models of pulmonary fibrosis in young adult and old mice and a model of adult alveologenesis after pneumonectomy, we show that administration of ISRIB, a small molecule that restores protein translation by EIF2B during activation of the integrated stress response (ISR), accelerated the differentiation of AT2 into AT1 cells. Accelerated epithelial repair reduced the recruitment of profibrotic monocyte-derived alveolar macrophages and ameliorated lung fibrosis. These findings suggest a dysfunctional role for the ISR in regeneration of the alveolar epithelium after injury with implications for therapy.

scholarly journals Lung injury induces alveolar type 2 cell hypertrophy and polyploidy with implications for repair and regeneration

2021 ◽  
Author(s):  
Anthea Weng ◽  
Mariana Maciel-Herrerias ◽  
Satoshi J Watanabe ◽  
Annette S. Flozak ◽  
Lynn Welch ◽  
...  
Keyword(s):  
Lung Injury ◽  
Ex Vivo ◽  
Alveolar Type ◽  
Lung Epithelium ◽  
Post Injury ◽  
Alveolar Epithelial ◽  
Cell Hypertrophy ◽  
Alveolar Epithelial Injury ◽  
Distal Lung

Epithelial polyploidization post-injury is a conserved phenomenon, recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces AT2 cell hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 trans-differentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response (ISR) using the small molecule ISRIB. These data suggest that AT2 polyploidization may be a feature of alveolar epithelial injury. As AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 self-renewal and regenerative potential upon re-injury, which may benefit from targeting the ISR.

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