Human airway submucosal gland organoids to study respiratory inflammation and infection
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ABSTRACT:
PROVIDER: PRJNA1129580 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR29647970_1.fastq.gz | Fastqsanger.gz | |||
| SRR29647970_2.fastq.gz | Fastqsanger.gz |
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Project description:The human airway lining consists of two physiologically distinct compartments: the surface airway epithelium (SAE) and the submucosal glands (SMGs). Despite their critical role, SMGs have remained largely overlooked in airway in vitro modeling of respiratory inflammation and infection. In this study, we leverage long-term cultured organoids derived separately from SAE and SMG to investigate their unique physiological characteristics. Single-cell RNA sequencing (scRNA-seq) analysis confirms that these organoid models accurately replicate the cellular heterogeneity inherent to each tissue type. Specifically, SMG organoids are enriched in MUC5B-producing mucous cells and generate alpha-Smooth Muscle Actin (αSMA)-expressing myoepithelial cells. We identify ANPEP/CD13 as a specific cell surface marker for SMG secretory cells. Exposure to cytokines elicits distinct transcriptomic responses in SMG secretory cells, providing insights into the cellular mechanisms underpinning inflammatory pathogenesis. Infection assays with human alpha-coronavirus 229E (HCoV-229E) reveal a selective vulnerability of CD13-positive secretory cells within SMG organoids, triggering a specific unfolded protein response associated with endoplasmic reticulum (ER) stress. These findings broaden the utility of airway organoids for precision modeling of respiratory (patho-)physiology
2025-06-12 | GSE271084 | GEO
Project description:The human airway lining consists of two physiologically distinct compartments: the surface airway epithelium (SAE) and the submucosal glands (SMGs). Despite their critical role, SMGs have remained largely overlooked in airway in vitro modeling of respiratory inflammation and infection. In this study, we leverage long-term cultured organoids derived separately from SAE and SMG to investigate their unique physiological characteristics. Single-cell RNA sequencing (scRNA-seq) analysis confirms that these organoid models accurately replicate the cellular heterogeneity inherent to each tissue type. Specifically, SMG organoids are enriched in MUC5B-producing mucous cells and generate alpha-Smooth Muscle Actin (αSMA)-expressing myoepithelial cells. We identify ANPEP/CD13 as a specific cell surface marker for SMG secretory cells. Exposure to cytokines elicits distinct transcriptomic responses in SMG secretory cells, providing insights into the cellular mechanisms underpinning inflammatory pathogenesis. Infection assays with human alpha-coronavirus 229E (HCoV-229E) reveal a selective vulnerability of CD13-positive secretory cells within SMG organoids, triggering a specific unfolded protein response associated with endoplasmic reticulum (ER) stress. These findings broaden the utility of airway organoids for precision modeling of respiratory (patho-)physiology
2025-06-12 | GSE271264 | GEO
Project description:The human airway lining consists of two physiologically distinct compartments: the surface airway epithelium (SAE) and the submucosal glands (SMGs). Despite their critical role, SMGs have remained largely overlooked in airway in vitro modeling of respiratory inflammation and infection. In this study, we leverage long-term cultured organoids derived separately from SAE and SMG to investigate their unique physiological characteristics. Single-cell RNA sequencing (scRNA-seq) analysis confirms that these organoid models accurately replicate the cellular heterogeneity inherent to each tissue type. Specifically, SMG organoids are enriched in MUC5B-producing mucous cells and generate alpha-Smooth Muscle Actin (αSMA)-expressing myoepithelial cells. We identify ANPEP/CD13 as a specific cell surface marker for SMG secretory cells. Exposure to cytokines elicits distinct transcriptomic responses in SMG secretory cells, providing insights into the cellular mechanisms underpinning inflammatory pathogenesis. Infection assays with human alpha-coronavirus 229E (HCoV-229E) reveal a selective vulnerability of CD13-positive secretory cells within SMG organoids, triggering a specific unfolded protein response associated with endoplasmic reticulum (ER) stress. These findings broaden the utility of airway organoids for precision modeling of respiratory (patho-)physiology
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Project description:Human airway submucosal gland organoids to study respiratory inflammation and infection [RNA-seq]
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Project description:Human airway submucosal gland organoids to study respiratory inflammation and infection [bulk RNA-seq]
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Project description:Background Human distal respiratory airway (DRA) cells are located in the smallest conducting airways of the human lung, specifically in the terminal and respiratory bronchioles, and represent a newly discovered cell type. Due to their absence in mice and the limited existing research on these cells, there is an urgent need to establish an in vitro model of human distal respiratory airways to study the role of such cells in respiratory diseases. Results Here, we developed a robust differentiation protocol to derive DRA organoids (DRAOs) from human pluripotent stem cells (hPSCs) and investigated their role in the treatment of chronic obstructive pulmonary disease (COPD). We engineered a cuboid chip-based culture platform, where seeding single-cell suspensions mixed with Matrigel onto the chip increased lung progenitor cell (LPC) spheroid yield by 7.5-fold and upregulated NKX2.1 expression nearly 300-fold. Single-cell transcriptomic analysis further demonstrated that the platform enhanced distal lung-related gene expression. Prolonged culture of LPC spheroids yielded expandable hollow lung organoids. The resulting cells exhibited protein and molecular profiles closely resembling native human DRA cells, with over 70% co-expressing SFTPB and SCGB3A2. Using this method, we demonstrate accelerated production of DRAOs with significantly enhanced structural and functional maturity in 30 days. Furthermore, these DRAOs retain the potential to undergo alveolar differentiation. By exposing these organoids to cigarette smoke extract (CSE), we established a COPD-like model. In addition, DRAOs can survive in COPD mice, repair alveolar structural damage, and alleviate COPD symptoms. Conclusions Our method will facilitate increasingly widespread culture and differentiation of organoids, paving the way for constructing more accurate models of complex organs that mimic in vivo structures and functions. Furthermore, the favorable applicability of DRAOs in cell therapy studies using a mouse model of COPD-related alveolar injury provides critical insights for cell therapy in respiratory diseases.
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