Adenoviral Vectors Transduce Alveolar Macrophages in Lung Cancer Models

Tippimanchai, D.; Nolan, Kyle; Poczobutt, Joanna M.; Verzosa, Gregory; Li, H.; Hannah, Sharon; DeGregori, James; Nemenoff, Raphael A.; Malkoski, Stephen P.

doi:10.1016/j.jtho.2017.06.056

Cited by 4 publications

(5 citation statements)

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“…6c, d); when the virus was instilled intratracheally into adult control mice (Fgfr2 +/fl ; Rosa26 mTmG/MASTR ), specific expression of Cre-dependent reporter genes was observed in AT2 cells (Fig. 6e; >98% of GFP + cells, n = 3 lungs, 168 GFP + cells counted per lung at 2 weeks), similar to the AT2 specificity observed in prior studies with this approach [38][39][40] . When the virus was instead instilled into Fgfr2 fl/fl ; Rosa26 mTmG/MASTR mice, 60% fewer GFP + AT2 cells were observed (Fig.…”

Section: Fgfr2 Signaling Continuously Prevents At2 Apoptosis During A...supporting

confidence: 81%

Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling

et al. 2022

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The lung’s gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. Fgfr2 is expressed in the developing progenitors in mouse then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of exogenous mechanical cues, induce progenitors to form alveolospheres with intermingled AT2 and AT1 cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 identity, whereas loss or inhibition later in life triggers AT2 apoptosis and compensatory regeneration. We propose that Fgfr2 signaling selects AT2 fate during development, induces a cell non-autonomous AT1 differentiation signal, then continuously maintains AT2 identity and survival throughout life.

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Section: Fgfr2 Signaling Continuously Prevents At2 Apoptosis During A...supporting

confidence: 81%

Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling

et al. 2022

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show abstract

“…6C,D); when the virus was instilled intratracheally into adult control mice (Fgfr2 +/fl ; Rosa26 mTmG/MASTR ), specific expression of Credependent reporter genes was observed in AT2 cells (>98% of GFP + cells, n = 3 lungs, >168 GFP + cells counted per lung (data not shown) at 2 weeks (Fig. 6E), similar to the AT2 specificity observed in prior studies with this approach 38,39,40 . When the virus was instead instilled into Fgfr2 fl/fl ; Rosa26 mTmG/MASTR mice, 60% fewer GFP + AT2 cells were observed (Fig.…”

Section: Fgfr2 Signaling Continuously Prevents At2 Apoptosis During Adult Lifesupporting

confidence: 84%

Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling

Brownfield

Arce

Ghelfi

et al. 2022

Preprint

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The lung's gas exchange surface comprises thin alveolar type 1 (AT1) cells and cuboidal surfactant-secreting AT2 cells that are corrupted in some of the most common and deadly diseases including adenocarcinoma, emphysema, and SARS/Covid-19. These cells arise from an embryonic progenitor whose development into an AT1 or AT2 cell is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. FGF Receptor 2 (Fgfr2) is expressed in mouse progenitors then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of differential mechanical cues, induce purified, uncommitted E16.5 progenitors to form alveolus-like structures with intermingled AT2 and AT1 cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 fate, whereas loss or inhibition later in life immediately triggers AT2 apoptosis followed by a compensatory regenerative response. We propose Fgfr2 signaling directly selects AT2 fate during development, induces a cell non-autonomous secondary signal for AT1 fate, and stays on throughout life to continuously maintain healthy AT2 cells.

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“…Primary immune cells such as macrophages or dendritic cells might also be employed to study Ad infection and antiviral responses. Low expression of CAR makes them difficult to infect , and their morphology is less convenient for imaging approaches although feasible . Choosing an appropriate cell model for Ad imaging thus depends on a balance between convenience of use and the biological question to be addressed.…”

Section: General Considerations When Imaging Admentioning

confidence: 99%

Imaging the adenovirus infection cycle

Pied

Wodrich

2019

FEBS Letters

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Edited by Urs GreberIncoming adenoviruses seize control of cytosolic transport mechanisms to relocate their genome from the cell periphery to specialized sites in the nucleoplasm. The nucleus is the site for viral gene expression, genome replication, and the production of progeny for the next round of infection. By taking control of the cell, adenoviruses also suppress cell-autonomous immunity responses. To succeed in their production cycle, adenoviruses rely on wellcoordinated steps, facilitated by interactions between viral proteins and cellular factors. Interactions between virus and host can impose remarkable morphological changes in the infected cell. Imaging adenoviruses has tremendously influenced how we delineate individual steps in the viral life cycle, because it allowed the development of specific optical markers to label these morphological changes in space and time. As technology advances, innovative imaging techniques and novel tools for specimen labeling keep uncovering previously unseen facets of adenovirus biology emphasizing why imaging adenoviruses is as attractive today as it was in the past. This review will summarize past achievements and present developments in adenovirus imaging centered on fluorescence microscopy approaches.Adenoviruses (Ads) are nonenveloped icosahedral viruses with a diameter of~90 nm with slight structural differences between genotypes. The majority of the Ad capsid shell is composed of 240 hexon trimers, and each of the 12 vertices of the icosahedron is occupied by a penton. Pentons are involved in cell attachment and receptor recognition and are composed of the pentameric penton base from which the trimeric fiber molecule extends. Minor capsid proteins IIIa, VI, VIII, and IX are embedded in the capsid and contribute to capsid stability. Protein VI is located at the inner surface of the capsid, and biochemical data suggest that it may connect the capsid to the core containing the viral genome via protein V. The genome is ã 36-kb double-stranded linear DNA molecule with the terminal protein (TP) covalently bound to each 5 0end. Adenovirus genomes are highly condensed and organized into chromatin by several hundred copies of Abbreviations ADP, adenovirus death protein

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Adenoviral Vectors Transduce Alveolar Macrophages in Lung Cancer Models

Cited by 4 publications

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Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling

Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling

Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling

Imaging the adenovirus infection cycle

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