p53 regulation by MDM2 contributes to self‐renewal and differentiation of basal stem cells in mouse and human airway epithelium

Garrido-Jimenez, Sergio; Barrera-Lopez, Juan Francisco; Diaz-Chamorro, Selene; Mateos-Quiros, Clara Maria; Rodriguez-Blanco, Ignacio; Marquez-Perez, Francisca Lourdes; Lorenzo, María Jesús López; Centeno, Francisco; Román, Ángel; Carvajal-González, José María

doi:10.1096/fj.202100638r

Cited by 12 publications

(10 citation statements)

References 53 publications

(124 reference statements)

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“…P53/P63 signaling responses to APM were identified by interrogation of dynamic TREs from PRO-seq and chromatin accessibility features from ATAC-seq, suggesting a combined signal-dependent and lineage-determining role for P53/P63 in small airway epithelia progenitor cells. This latter function aligns with numerous previous studies of the airway epithelia (43, 44, 46, 48), however, the integrated role of this family in exposure responses has not been reported to our knowledge. The combined role may reflect differential activity of distinct P53/P63 family members or the effects of transcription factors that cooperate with P53/P63.…”

Section: Discussionsupporting

confidence: 92%

Integrated Genomics Approaches Identify Transcriptional Mediators and Epigenetic Responses to Afghan Desert Particulate Matter in Small Airway Epithelial Cells

Gupta

Sasse

Berman

et al. 2022

Preprint

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New respiratory diseases in personnel deployed to Southwest Asia after September 11th raise major concerns about the impacts of airborne particulate matter. Although regulations exist, the knowledge about how particulates influence disease states is limited, precluding the appropriate recognition, prevention and treatment of deployment-related lung diseases. We applied two genomics assays, Precision Run-on sequencing (PRO-seq) and the assay for transposase accessible chromatin with sequencing (ATAC-seq), to characterize the small airway epithelial cell response to Afghan desert particulate matter (APM). In addition to cellular pathways that regulate susceptibility to further insults, such as cytochrome P450 or P53, we identified novel pathways associated with APM exposure, such as GRHL2 loss or TEAD3 activation. We further demonstrated that TEAD3 activation was unique to APM exposure despite similar inflammatory responses when compared with wood smoke particle (WSP) exposure. Our results establish the utility of an integrated genomics approach in characterizing responses to exposures and identify cellular and genomic targets for advanced investigation of the pathogenesis of deployment-related respiratory disease.

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Section: Discussionsupporting

confidence: 92%

Integrated Genomics Approaches Identify Transcriptional Mediators and Epigenetic Responses to Afghan Desert Particulate Matter in Small Airway Epithelial Cells

Gupta

Sasse

Berman

et al. 2022

Preprint

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“…To establish the potential cytotoxic effect of those different products, we started by assessing their impact on basal stem cell proliferation. Basal stem cells are responsible for airway epithelia regeneration producing secretory cells and ciliated cells through a cell differentiation process [ 22 , 23 ]. We used primary airway basal epithelial cells to measure cell proliferation under different culture conditions.…”

Section: Resultsmentioning

confidence: 99%

“…We started by characterizing a Pasteurella multocida infection in mouse tracheal epithelial cells (MTECs). By using the same approach developed by Garrido-Jimenez et al in 2021 [ 23 ], we exposed fully differentiated airway epithelial cells to P. multocida for 4 h and allowed the epithelial response for 12 additional hours (Figure 3 A). After 16 h, we did not find any significant difference in the epithelial barrier function of the epithelia, measured by TEER (Additional file 2 ).…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells

Bravo,

Diaz-Chamorro,

Garrido-Jiménez

et al. 2023

Vet Res

Self Cite

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The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.

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“…Loss of Lef-1 significantly reduces the regenerative capability of BSC following injury [57]. The inactivation of p53 promotes BSCs self-renewal in vitro [58], and direct inhibition of the MDM2/p53 interaction, which increases the p53 expression level, antagonizes the differentiation process in BSCs [59]. Mature BSCs also maintain moderate Id2 expression to sustain proliferative potential, and TGF-β signaling regulates tissue regeneration through recurrent Id2 activation following injury [60].…”

Section: Signaling Pathways Involved In Bscs Related Airway Repair An...mentioning

confidence: 99%

Roles of airway basal stem cells in lung homeostasis and regenerative medicine

Zhang

Lin

et al. 2022

Respir Res

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Airway basal stem cells (BSCs) in the proximal airways are recognized as resident stem cells capable of self-renewing and differentiating to virtually every pseudostratified epithelium cell type under steady-state and after acute injury. In homeostasis, BSCs typically maintain a quiescent state. However, when exposed to acute injuries by either physical insults, chemical damage, or pathogen infection, the remaining BSCs increase their proliferation rate apace within the first 24 h and differentiate to restore lung homeostasis. Given the progenitor property of airway BSCs, it is attractive to research their biological characteristics and how they maintain homeostatic airway structure and respond to injury. In this review, we focus on the roles of BSCs in lung homeostasis and regeneration, detail the research progress in the characteristics of airway BSCs, the cellular and molecular signaling communications involved in BSCs-related airway repair and regeneration, and further discuss the in vitro models for airway BSC propagation and their applications in lung regenerative medicine therapy.

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p53 regulation by MDM2 contributes to self‐renewal and differentiation of basal stem cells in mouse and human airway epithelium

Cited by 12 publications

References 53 publications

Integrated Genomics Approaches Identify Transcriptional Mediators and Epigenetic Responses to Afghan Desert Particulate Matter in Small Airway Epithelial Cells

Integrated Genomics Approaches Identify Transcriptional Mediators and Epigenetic Responses to Afghan Desert Particulate Matter in Small Airway Epithelial Cells

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells

Roles of airway basal stem cells in lung homeostasis and regenerative medicine

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