Spatiotemporal Expression of Three Secretoglobin Proteins, SCGB1A1, SCGB3A1, and SCGB3A2, in Mouse Airway Epithelia

Naizhen, Xu; Kido, Taketomo; Yokoyama, Shigetoshi; Linnoila, R. Ilona; Kimura, Shioko

doi:10.1369/0022155419829050

Cited by 27 publications

(18 citation statements)

References 41 publications

(77 reference statements)

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“…3E+G). Interestingly, SCGB3A1 and SCGB3A2 , two genes that were previously associated with lung development [17], positively correlated with this dimension (Supp. Fig.…”

Section: Resultsmentioning

confidence: 95%

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Bischoff

Trinks

Obermayer

et al. 2020

Preprint

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Recent developments in immuno-oncology demonstrate that not only cancer cells, but also features of the tumor microenvironment guide precision medicine. Still, the relationship between tumor and microenvironment remains poorly understood. To overcome this limitation and identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to lung adenocarcinomas. While the highly heterogeneous carcinoma cell transcriptomes reflected histological grade and activity of relevant oncogenic pathways, our analysis revealed two distinct microenvironmental patterns. We identified a prognostically unfavorable group of tumors with a microenvironment composed of cancer-associated myofibroblasts, exhausted CD8+ T cells, proinflammatory monocyte-derived macrophages and plasmacytoid dendritic cells (CEP2 pattern) and a prognostically favorable group characterized by myeloid dendritic cells, anti-inflammatory monocyte-derived macrophages, normal-like myofibroblasts, NK cells and conventional T cells (MAN2C pattern). Our results show that single-cell gene expression profiling allows to identify patient subgroups based on the tumor microenvironment beyond cancer cell-centric profiling.

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“…3E+G). Interestingly, SCGB3A1 and SCGB3A2 , two genes that were previously associated with lung development [17], positively correlated with this dimension (Supp. Fig.…”

Section: Resultsmentioning

confidence: 95%

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Bischoff

Trinks

Obermayer

et al. 2020

Preprint

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“…6A). At E18.5, most epithelial cells in distal bronchioles of normal murine lungs are non-ciliated cuboidal cells positive for SCGB1A1 77 . We quantified the total number of SCGB1A1+ and FOXJ1+ cells and calculated the ratio of these cells in the terminal bronchioles of normal and mutant lungs.…”

Section: Resultsmentioning

confidence: 99%

Svep1 orchestrates distal airway patterning and alveolar differentiation in murine lung development

Foxworth

Wells

Ocana-Lopez

et al. 2021

Preprint

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Proper lung development and function requires two independent but interrelated processes: branching morphogenesis to form the airway tree, and alveolar cell differentiation for peripheral gas exchange. The disruption of either branching or differentiation results in severe respiratory deficiencies and often in neonatal death. The molecular mechanisms that control branching patterns and the transition to alveolar differentiation are not completely understood. Here we report on the in vitro and in vivo characterization of the lungs of mouse embryos lacking a functional Svep1 gene. Our data demonstrate that the SVEP1 extracellular matrix protein is critical for the process of transitioning from branching to alveolar maturation. Svep1-/- embryos on a C57BL/6J genetic background are characterized by hypoplastic lungs and a disorganized increase in distal airway tips which disrupts airway architecture and lobe shape. The lungs of Svep1 knockout embryos also have defects in alveolar differentiation. In vitro lung explant experiments demonstrated that SVEP1 normally inhibits branching morphogenesis and that treatment with a SVEP1 peptide can rescue the branching defects observed in Svep1 knockouts. Our findings reveal for the first time that Svep1 is essential for constructing the basic airway architecture and for the transition from lung branching to alveolar differentiation. Our results suggest therapeutic strategies to enhance lung development in patients with life-threatening respiratory disorders such as the lung hypoplasia and prematurity observed in neonates with congenital diaphragmatic hernia (CDH).

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“…SCGB3A1 belong to secretoglobin gene superfamily, which are cytokine-like small molecular weight secreted proteins and predominantly expressed in lung airway epithelial cells 31 . Secretoglobins are thought to be involved in immunomodulatory 32 . Moreover, SCGB3A1…”

Section: Discussionmentioning

confidence: 99%

Clinical and Prognostic Implications of an Immune-Related Risk Model Based on TP53 Status in Lung Adenocarcinoma

Song

Chen

Wang

et al. 2020

Preprint

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Background: TP53 mutation is the most widespread mutation in lung adenocarcinoma (LUAD), meanwhile p53 (encoded by TP53) has recently been implicated in immune responses. However, it is still unknown whether TP53 mutation may remodel tumor microenvironment to influence tumor progression and prognosis in LUAD.Methods: we developed a six-gene immune-related model (IRM) to predict the survival of patients with LUAD in TCGA cohort based on TP53 status using LASSO Cox analysis, which was also confirmed the predictive ability in two independent cohorts.Results: The mutation of TP53 led to a decrease in the immune response in LUAD. Further analysis revealed that patients in the high-index group had observably lower relative infiltration of memory B cells and regulatory T cells, together with significantly higher relative infiltration proportions neutrophils and resting memory CD4+ T cells. Additionally, the IRM index positively correlated with expression of critical immune checkpoint genes including PDCD1 (encoding PD-1) and CD274 (encoding PD-L1), which was validated in Nanjing cohort. Furthermore, the IRM index as an independent prognostic factor was used to establish a nomogram for clinical application.Conclusion: This immune-related model may serve as a powerful prognostic tool to further optimize immunotherapies for LUAD.

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Spatiotemporal Expression of Three Secretoglobin Proteins, SCGB1A1, SCGB3A1, and SCGB3A2, in Mouse Airway Epithelia

Cited by 27 publications

References 41 publications

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Svep1 orchestrates distal airway patterning and alveolar differentiation in murine lung development

Clinical and Prognostic Implications of an Immune-Related Risk Model Based on TP53 Status in Lung Adenocarcinoma

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