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opencc-zeroMar 2024View details →

Data from: Gastrointestinal gd T cells reveal upregulated T-cell transcripts and signaling pathways during peanut oral immunotherapy

Oral immunotherapy (OIT) has been successful in desensitizing patients to offending food allergens, although identification of tissue-resident T cell subsets and cognate pathways leading to desensitization has been challenging. The T cells are a major T-cell subset of mucosal intraepithelial lymphocytes (IELs) and play a significant role in tissue homeostasis and repair. Studies in mouse models suggested a regulatory role of gd T cells in food allergy (FA). Also, peripheral gd T cells from patients analyzed over 24 weeks of peanut OIT were shown to undergo dynamic changes in expression profiles, implicating pathways involved in immune homeostasis. To our knowledge, the role of gd T cells in the intestinal mucosa of FA patients during immunotherapy has not been examined. To this end, we investigated whether gd T cells in the gastrointestinal (GI) tract are modulated during peanut OIT. We hypothesized that GI-resident gd T cells in FA patients would increase during the course of peanut OIT and reveal transcripts and pathways relevant to the mechanisms of peanut desensitization.

opencc-zeroApr 2024View details →

Replication Data for: Precision Oncology, Cell Signaling and Targeted Therapy: A Holistic Approach to Molecular Cancer Therapeutics

In recent decades, there has been a deluge in the large-scale production of anticancer agents, primarily due to advances in genomic technologies enabling precise targeting of oncogenic pathways involved in disease progression. This initiated a paradigm shift in cancer research and therapeutics based on the ability to study molecular changes throughout the genome. It provided a unique opportunity in the field of translational cancer research and have led to the concept of precision medicine in cancer therapy, raising hopes of developing better diagnostic and therapeutic means for the management of cancer. The purpose of this article is to briefly review the tools and techniques involved in precision oncology research and their applications in the field of cancer treatment.

opencc-zeroSep 2022View details →

Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19

The biological determinants underlying the range of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Examination of informative model features reveals novel biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.

opencc-zeroMay 2024View details →

Scaling between cell cycle duration and wing growth is regulated by Fat-Dachsous signaling in Drosophila

The atypical cadherins Fat and Dachsous (Ds) signal through the Hippo pathway to regulate growth of numerous organs, including the Drosophila wing. Here, we find that Ds-Fat signaling tunes a unique feature of cell proliferation found to control the rate of wing growth. The duration of the cell cycle increases in direct proportion to the size of the wing, leading to linear rather than exponential growth. Ds-Fat signaling enhances the rate at which the cell cycle lengthens with wing size, thus diminishing the linear rate of wing growth. We show that this results in a complex but stereotyped relative scaling of wing growth with body growth in Drosophila. Finally, we examine the dynamics of Fat and Ds protein distribution in the wing, observing graded distributions that change during growth. However, the significance of these dynamics is unclear since perturbations in expression have negligible impact on wing growth.

opencc-by-4.0Aug 2024View details →

Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling: single cell RNA sequencing data

Meningeal single cell RNA sequencing data Meningeal samples were collected from both dorsal and ventral skull, avoiding inclusion of choroid plexus. Samples were digested in 2.5 mg/mL Collagenase D (Cat. #11088858001; Roche) and 12.5 μL of 0.5 mg/mL DNAseI (Cat. #L5002139; Worthington), put on a shaker at 370C for 30 m, diluted with cold HBSS + 0.1% BSA, and mashed through a 70 μm cell strainer prior to sorting. Data represent live, nucleated, singlet cells (DAPI-DRAQ5+) sorted on a BD FACS Aria Fusion into HBSS + 10% FBS prior to droplet encapsulation using 10x Genomics’ Drop-seq platform (Chromium v2). 10X chip lane is indicate by 'group' column Group 1 = 4 pooled homecage control (unstressed) mice Group 2 = 4 pooled homecage control (unstressed) mice Group 3 = 4 pooled mice exposed to chronic social defeat for 14 days; tissue was collected 2 hours following final defeat See the following repositories for data processing: <a href="https://github.com/maryellenlynall/2019_bcell_stress/blob/master/bcellstress20.Rmd">https://github.com/maryellenlynall/2019_bcell_stress/</a> (processing from raw files starts at bcellstress020.Rmd) <a href="https://github.com/staceykigar/meningeal_neut/">https://github.com/staceykigar/meningeal_neut/</a> We also provide a processed dataset (processed.RData) with assays 'counts' and 'logcounts' which is the processed single cell object saved at line "# Save object for upload to Zenodo" in script <a href="https://github.com/staceykigar/meningeal_neut/">https://github.com/staceykigar/meningeal_neut/</a>neutrophilstress01.Rmd  Cluster annotations are in sce$Annotation Neutrophil subcluster annotations are in sce$Subcluster Sample condition is in sce$cond, where "HC" indicates homecage control and "SD" indicates chronic social defeat 10X chip lane is in sce$group

opencc-zeroDec 2022View details →

Soluble T-cadherin promotes pancreatic β-cell proliferation by upregulating Notch signaling

Endogenous humoral factors that link systemic and/or local insulin demand to pancreatic β-cells have not been identified. Here, we demonstrated that T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin primarily expressed in vascular endothelial cells and cardiac and skeletal muscle cells, but not in pancreatic β-cells, was secreted as soluble forms and was important for β-cell proliferation. Cdh13 (T-cadherin) knockout mice exhibited impaired glucose handling due to attenuated β-cell proliferation under high-fat diet conditions. The gene expression analyses indicated the impairment in cell cycle and Notch signaling in the islets of T-cadherin knockout mice under high-fat diet conditions. In streptozotocin-induced diabetes, the replacement of soluble T-cadherin improved β-cell mass and blood glucose levels in T-cadherin knockout mice. Recombinant soluble T-cadherin upregulated Notch signaling in cultured murine islets. We concluded that soluble T-cadherin could work as an endogenous humoral factor whose signaling pathways including Notch signaling regulate β-cell proliferation under diabetic conditions in mice.

opencc-by-4.0Jan 2023View details →

Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle

Succinate is released by skeletal muscle during exercise and activates SUCNR1/GPR91. Signaling of SUCNR1 is involved in cell-cell communication in skeletal muscle. However, the specific cell types responding to succinate and the directionality of communication are unclear. De novo analysis of transcriptomic datasets demonstrated that SUCNR1 mRNA is expressed in immune, adipose, and liver tissues, but scarce in skeletal muscle. In human tissues, SUCNR1 mRNA was associated with macrophage markers. Single-cell RNA sequencing and fluorescent RNAscope demonstrated that in human skeletal muscle, SUCNR1 mRNA is not expressed in muscle fibers but coincided with macrophage populations. Human M2-polarized macrophages exhibit high levels of SUCNR1 mRNA and stimulation with selective agonists of SUCNR1 triggered Gq- and Gi-coupled signaling. Primary human skeletal muscle cells were unresponsive to SUCNR1 agonists. In conclusion, SUCNR1 is not expressed in muscle cells and its role in the adaptive response of skeletal muscle to exercise is most likely mediated via paracrine mechanisms involving M2-like macrophages within the muscle.

opencc-by-4.0Mar 2022View details →

The EGFR signaling modulates in mesenchymal stem cells the expression of miRNAs involved in the interaction with breast cancer cells

We previously demonstrated that the epidermal growth factor receptor (EGFR) modulates in mesenchymal stem cells (MSCs) the expression of a number of genes coding for secreted proteins that promote breast cancer progression. However, the role of the EGFR in modulating in MSCs the expression of miRNAs potentially involved in the progression of breast cancer remains largely unexplored. Following small RNA-sequencing, we identified 36 miRNAs differentially expressed between MSCs untreated or treated with the EGFR ligand transforming growth factor α (TGFα), with a fold change (FC) <0.56 or FC ≥1.90 (CI, 95%). KEGG analysis revealed a significant enrichment in signaling pathways involved in cancer development and progression. EGFR activation in MSCs downregulated the expression of different miRNAs, including miR-23c. EGFR signaling also reduced the secretion of miR-23c in conditioned medium from MSCs. Functional assays demonstrated that miR-23c acts as tumor suppressor in basal/claudin-low MDA-MB-231 and MDA-MB-468 cells, through the repression of IL-6R. MiR-23c downregulation promoted cell proliferation, migration and invasion of these breast cancer cell lines. Collectively, our data suggested that the EGFR signaling regulates in MSCs the expression of miRNAs that might be involved in breast cancer progression, providing novel information on the mechanisms that regulate the MSC-tumor cell cross-talk.We previously demonstrated that the epidermal growth factor receptor (EGFR) modulates in mesenchymal stem cells (MSCs) the expression of a number of genes coding for secreted proteins that promote breast cancer progression. However, the role of the EGFR in modulating in MSCs the expression of miRNAs potentially involved in the progression of breast cancer remains largely unexplored. Following small RNA-sequencing, we identified 36 miRNAs differentially expressed between MSCs untreated or treated with the EGFR ligand transforming growth factor α (TGFα), with a fold change (FC) <0.56 or FC ≥1.90 (CI, 95%). KEGG analysis revealed a significant enrichment in signaling pathways involved in cancer development and progression. EGFR activation in MSCs downregulated the expression of different miRNAs, including miR-23c. EGFR signaling also reduced the secretion of miR-23c in conditioned medium from MSCs. Functional assays demonstrated that miR-23c acts as tumor suppressor in basal/claudin-low MDA-MB-231 and MDA-MB-468 cells, through the repression of IL-6R. MiR-23c downregulation promoted cell proliferation, migration and invasion of these breast cancer cell lines. Collectively, our data suggested that the EGFR signaling regulates in MSCs the expression of miRNAs that might be involved in breast cancer progression, providing novel information on the mechanisms that regulate the MSC-tumor cell cross-talk.

opencc-zeroMay 2023View details →

Data from: The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipocyte cell size

Defective nutrient storage and adipocyte enlargement (hypertrophy) are emerging features of metabolic syndrome and type 2 diabetes. How the cytoskeletal network contributes to nutrient uptake, fat storage, and adipocyte size remains poorly understood. Utilizing the Drosophila larval fat body (FB) as a model adipose tissue, we show that a specific actin isoform—Act5C—forms the cortical actin network necessary for inter-organ lipid trafficking. Act5C also promotes FB tissue expansion during larval development so larvae can store sufficient biomass for metamorphosis. We find FB-specific loss of Act5C, but not other Drosophila actins, perturbs FB triglyceride (TG) storage in lipid droplets (LDs), resulting in developmentally delayed larvae that fail to develop into flies. Act5C localizes to the FB cell surface where it intimately contacts peripheral LDs (pLDs), forming a cortical actin network together with spectrins for cell architectural support. While both the cortical actin and spectrin cytoskeletons maintain FB cell surface architecture, we find that only the actin network is required for fat storage. Mechanistically, we show that FBs lacking the Act5C cortical cytoskeleton exhibit a block in lipoprotein (Lpp) secretion from FB cells, and a subsequent disruption of gut:FB inter-organ lipid transport, resulting in mid-gut fat accumulation. Utilizing temporal RNAi-depletion approaches, we also reveal that Act5C is indispensable post-embryogenesis during larval feeding to promote FB cell expansion. Act5C-deficient FBs fail to expand cell sizes, leading to lipodystrophic larvae unable to accrue sufficient biomass for metamorphosis. Collectively, we propose that the Act5C-mediated cortical actin network of Drosophila adipose tissue plays an essential role in post-embryonic inter-organ nutrient transport and FB cell size determination for organismal energy homeostasis and development.

controlledIPD-YESFeb 2026View details →

A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia (CLL) Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor The

ClinicalTrials.gov study NCT02141282. IPD Sharing: YES. Countries: 1. Publications: 3.

restrictedIPD-UNDECIDEDFeb 2026View details →

Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas

ClinicalTrials.gov study NCT02030834. IPD Sharing: Not stated. Countries: 1. Publications: 2.

closedIPD-NOFeb 2026View details →

Effects of Growth Hormone and IGF-1 on Anabolic Signals and Stem Cell Recruitment in Human Skeletal Muscle

ClinicalTrials.gov study NCT03878992. IPD Sharing: NO. Countries: 1. Publications: 12.

restrictedIPD-UNDECIDEDFeb 2026View details →

Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia

ClinicalTrials.gov study NCT02030847. IPD Sharing: Not stated. Countries: 1. Publications: 1.