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GSE197751
Homo sapiens
18 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
Chronic obstructive pulmonary disease (COPD) is a heterogenous respiratory disease mainly caused by smoking. Respiratory infections constitute a major risk factor for acute worsening of COPD symptoms or COPD exacerbation. Mitochondrial functionality, which is crucial for the execution of physiologic functions of metabolically active cells, is impaired in airway epithelial cells (AECs) of COPD patients as well as smokers. However, the potential contribution of mitochondrial dysfunction in AECs to progression of COPD, infection-triggered exacerbations in AECs and a potential mechanistic link between mitochondrial and epithelial barrier dysfunction is unknown to date. In this study, we used an in vitro COPD exacerbation model based on AECs exposed to cigarette smoke extract (CSE) followed by infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress, as an indicator of mitochondrial stress were quantified upon CSE and Sp. The expression of proteins associated with mitophagy, mitochondrial content and biogenesis as well as mitochondrial fission and fusion was quantified upon CSE and Sp. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with mitochondrial function. We found that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp and may thus trigger COPD exacerbation.
Publication Title
Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative
Publication Title
The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
To elucidate the mechanism of BCL6-mediated pre-B cell survival signaling, we investigated the gene expression pattern in BCR-ABL1-transformed BCL6+/+ and BCL6-/- B cell precursors. Pharmacological inhibition of BCR-ABL1 was performed with the BCR-ABL1 kinase inhibitor STI571 (Imatinib).
Publication Title
BCL6 is critical for the development of a diverse primary B cell repertoire.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) can be subdivided into different categories based on genetic abnormalities.
Publication Title
Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
Description
The transcription factor STAT5 plays a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we demonstrate that STAT5 activation cooperates with defects in the pre-BCR signaling components encoded by Blnk, Btk, Prkcb, Nfkb1, and Ikzf1 to initiate B-ALL. STAT5 antagonizes NF-B and IKAROS by opposing regulation of shared target genes. STAT5 binding was enriched at super-enhancers, which were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4, and IKAROS. Patients with high ratios of active STAT5 to NF-B or IKAROS have more aggressive disease. Our studies illustrate that an imbalance of two opposing transcriptional programs drive B-ALL, and suggest that restoring the balance of these pathways may inhibit B-ALL.
Publication Title
Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.
Sample Metadata Fields
No sample metadata fields
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