Culture conditions differentially regulate the inflammatory niche and cellular phenotype of tracheobronchial basal stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA930392 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23302823_1.fastq.gz | Fastqsanger.gz | |||
| SRR23302823_2.fastq.gz | Fastqsanger.gz | |||
| SRR23302824_1.fastq.gz | Fastqsanger.gz | |||
| SRR23302824_2.fastq.gz | Fastqsanger.gz | |||
| SRR23302825_1.fastq.gz | Fastqsanger.gz |
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Project description:Bronchial epithelial cells derived from the tracheobronchial regions of human airways (HBECs) provide a valuable in vitro model for studying pathological mechanisms and evaluating therapeutics. This cell population comprises a mixed population of basal cells (BCs), the predominant stem cell in airways capable of both self-renewal and functional differentiation. Despite their potential for regenerative medicine, BCs exhibit significant phenotypic variability in culture. To investigate how culture conditions influence BC phenotype and function, we expanded three independent BC isolates in three media: airway epithelial cell growth medium (AECGM), dual-SMAD inhibitor (DSI)-enriched AECGM, and PneumaCult Ex plus (PEx+). Analysis through RNA sequencing, immune assays, and impedance measurements revealed that PEx+ media significantly drove cell proliferation and a broad proinflammatory phenotype in BCs. In contrast, BCs expanded in AECGM and displayed increased expression of structural and extracellular matrix components at higher passage. AECGM increased expression of some cytokines at high passage, whereas DSI suppressed inflammation implicating the involvement TGF-β in BC inflammatory processes. Differentiation capacity of BCs declined with time in culture irrespective of expansion media. This was associated with an increase in PLUNC expressing secretory cells in AECGM and PEx+ media consistent with the known immune modulatory role of PLUNC in the airways. These findings highlight the profound impact of media conditions on inflammatory niche established by, and function of, in vitro expanded BCs. The broad proinflammatory phenotype driven by PEx+ media, in particular, should be considered in the development of cell-based models for airway diseases and therapeutic applications.NEW & NOTEWORTHY Airway basal cells, vital for airway regeneration and potential therapies, show significant changes based on culture conditions. Our study reveals that media composition and culture duration greatly affect basal cell properties with profound changes in the proinflammatory phenotype and extracellular matrix deposition driven by changes in growth conditions. These results underscore the critical impact of culture conditions on BC phenotype, influencing cell-based models for airway disease research and therapy.
2025-06-20 | GSE224243 | GEO
Project description:Human bronchial epithelial cells (HBECs) derived from the tracheo-bronchial regions of human airways provide an excellent in vitro model for studying pathological mechanisms and evaluating therapeutics in human airway cells. This cell population comprises a mixed population of basal cells (BCs), the predominant stem cell in airways capable of both self-renewal and functional differentiation. Despite their potential for regenerative medicine, BCs exhibit significant phenotypic variability in culture. To investigate how culture conditions influence BC phenotype and function, we expanded three independent BC isolates in three media, airway epithelial cell growth medium (AECGM), dual-SMAD inhibitor (DSI)-enriched AECGM, and Pneumacult Ex plus (PEx+). Extensive RNA sequencing, immune assays and electrical measurements revealed that PEx+ media significantly drove cell proliferation and a broad pro-inflammatory phenotype in BCs. In contrast, BCs expanded in AECGM, displayed increased expression of structural and extracellular matrix components at high passage. Whereas culture in AECGM increased expression of some cytokines at high passage, DSI suppressed inflammation altogether thus implicating TGF-β in BC inflammatory processes. Differentiation capacity declined with time in culture irrespective of expansion media except for PLUNC expressing secretory cells that were elevated at high passage in AECGM and PEx+ suggestive of an immune modulatory role of PLUNC in BCs. These findings underscore the profound impact of media conditions on inflammatory niche and function of in vitro expanded BCs. The broad pro-inflammatory phenotype driven by PEx+ media, in particular, should be considered in the development of cell-based models for airway diseases and therapeutic application.
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Project description:Next-generation sequencing of mRNA extracted from immature tracheobronchial basal cells and their differentiated structures from air-liquid interface (ALI) was performed to quantitatively analyze TO-associated changes at transcriptional levels. RNA-Seq data revealed distinct expression profiles and divergent fate commitments between normal tissue-derived and TO lesion region-derived basal cells. In particular, there were 339 genes up-regulated at stem cell state and 1266 up-regulated upon differentiation (cutoff at fold change>2, p<0.05) in TO, whilst 173 TO-associated down-regulated genes and 1646 genes with reduced expression (cutoff at fold change<-2, p<0.05) were detected before and after differentiation respectively, compared to normal controls. Our results show that TO-derived basal cells, although exhibit high similarities on clone morphology and key marker staining, are transcriptionally different from normal tissue-derived counterpart and possess altered multipotency evidenced by transcriptome characterization. To further evaluate airway basal cell conditions in lesion-free regions of TO patients, RNA-Seq data was generated on cultured TBBCs derived from patient-matched (PM) relatively normal regions, and their ALI differentiated structures. Compared to stem cell state, there were 3314 genes induced in expression whilst 1627 down-regulated in the process of PM-TBBCs differentiation. Distinct differentiation-induced gene expression patterns were detected across TO patients, indicating a change of basal cell condition from normal mucociliary-committed status to a more disease-prone, inflammatory state during TO progression, and such basal cell alteration appeared prior to nodule formation.
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Project description:Transcriptional and epigenetic profiling of tracheobronchial basal cells derived from patients with Tracheobronchopathia Osteochondroplastica (TO)
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Project description:RNA isolated from draining tracheobronchial lymph nodes (TBLN) from 5-week old pigs, either clinically infected with a feral isolate of Pseudorabies virus or uninfected were interrogated using Illumina Digital Gene Expression Tag Profiling. Over 100 million tag sequences were observed, representing 4,064,189 unique 21-base sequences collected from TBLN at time points 1, 3, 6 and 14 days post-infection (dpi) RNA isolated from draining tracheobronchial lymph nodes (TBLN) from 5-week old pigs (% per group pooled), either clinically infected with feral isolate FS268 of Pseudorabies virus or uninfected at 1, 3, 6, and 14 days post inoculation. Over 100 million tag sequences were observed, representing 4,064,189 unique 21-base sequences.
2015-10-30 | E-GEOD-74473 | biostudies-arrayexpress
Project description:Epithelial barriers are programmed for defense and repair but are also frequently the site of long-term remodeling disease. In general, this paradigm features activation of epithelial stem cells that coordinate organ development but persist into adult life to regenerate damaged tissues. Here we identify a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functions as an early sentinel niche for basal-epithelial stem cells (basal-ESC) growth and feed-forward inflammation in mouse models of epithelial injury due to respiratory viral infections. This niche function depends on Gpnmb-CD44 signaling so that transient but properly timed antibody blockade of ligand or receptor provides long-lasting disease correction in these injuries. These same control points are found for mouse and human basal-ESC-derived organoids, and the corresponding biomarkers track with comparable lung diseases in humans. Together, the findings identify a mechanism to explain and modify basal-ESC reprogramming in what is otherwise a stereotyped, primordial response to epithelial injury.
2025-04-11 | GSE263930 | GEO
Project description:Dissemination of cancer stem cells (CSCs) serves as the basis of metastasis. Recently, we demonstrated that circulating prostate cancer (PCa) targets the hematopoietic stem cell (HSCs) ‘niche’ in marrow during dissemination. Once in the niche, disseminated tumor cells (DTCs) may remain dormant for extended periods. As the major function of the HSC niche is to maintain stem cell functions, we hypothesized that the niche regulates CSC activities of DTCs. We show that DTCs recovered from marrow were significantly enriched for a CSC phenotype. Critically, the conversion of DTCs to CSCs is regulated by niche. The data demonstrate that the niche plays a significant role in maintaining tumor-initiating PCa in marrow and suggests a functional relationship between CSCs and dormancy. Understanding how the marrow niche regulates the conversion of DTCs to CSCs is critical for the development of therapeutics specifically targeting skeletal bone metastasis and dormancy. We used microarrays to determine the global changes in gene expression underlying the significant roles of the marrow niche in activating cancer stem-like cell programs of prostate caner.
2016-01-30 | GSE77379 | GEO
Project description:Breast cancer is a heterogeneous disease comprised of at least five major subtypes. Luminal subtype tumors confer a more favourable patient prognosis, which is in part, attributed to the Estrogen Receptor-alpha (ER) positivity and anti-hormone responsiveness of these tumors. Expression of the forkhead box transcription factor, FOXA1, also correlates with the luminal subtype and patient survival, but is present in a subset of ER-negative tumors. Similarly, FOXA1 is consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, basal breast cancer cell lines do not express FOXA1, and loss of FOXA1 in luminal cells increases migration and invasion, characteristics of the basal subtype. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favourable prognosis, we performed cDNA microarray analyses on luminal FOXA1-positive, ER-positive (MCF7, T47D) and FOXA1-positive, ER-negative (MDA-MB-453, SKBR3) cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal-signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Use of Gene Set Enrichment Analyses (GSEA) as a phenotyping tool revealed that FOXA1 silencing resulted in a transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to both luminal and basal genes within luminal breast cancer cells, suggesting that it not only transactivates luminal genes, but also represses basal-associated genes. From these results we conclude that FOXA1 controls plasticity between basal and luminal cells, playing a dominant role in repressing the basal phenotype, and thus tumor aggressiveness, in luminal breast cancer cells. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward a more aggressive cancer. FOXA1 siRNA treated breast cell lines compared directly to nonspecific siRNA treated cell lines using Agilent 4X44 microarrays.
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Project description:To progress, tumors need to invade the surrounding tissues. However, the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insights for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas (BCCs), we define the cellular contributors of the invasive front. In the invasive niche, tumor cells harbor a collective migration phenotype, supported by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts (CAFs) with extracellular matrix-remodeling features, as required to support collective migration. Moreover, while tumor cells specifically express Activin A, we find Activin A-induced gene signature enrichment in adjacent CAFs subpopulations, further supporting their biological crosstalk. Altogether, our data identify the subpopulations and their transcriptional reprogramming contributing to the spatial organization of the BCC invasive niche. They also bring the proof-of-concept for integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop therapeutic targeting.
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