Intracellular and Extracellular Vesicle miRNA Signatures in Human iPSC-Derived Neural Stem Cells and Floor Plate Progenitors.

Refined control of intrinsic and extrinsic signals is critical for specific neuronal differentiation. Here, we differentiated human induced pluripotent stem cells (hiPSCs) from three different healthy donors into neural stem cells (NSCs) and floor plate progenitors (FPPs; progenitors of dopaminergic neurons) and further performed intracellular and extracellular vesicles' (EVs) miRNA profiling. While NSC and FPP cells differed significantly in levels of only 8 intracellular miRNAs, their differences were more evident in the EV miRNAs with 27 differentially expressed miRNAs.

Modulation of neuroimmune cytokine networks by antidepressants: implications in mood regulation.

Major Depressive Disorder (MDD) is increasingly recognized as a neuroinflammatory condition characterized by dysregulated cytokine networks. This comprehensive review examines the immunomodulatory effects of antidepressant medications, revealing their significant impact on Th1/Th2 cytokine balance beyond their classical neurotransmitter actions. Clinical data show that diverse antidepressant classes consistently demonstrate immunomodulatory properties that extend beyond their classical neurotransmitter effects.

Low-dose methotrexate as a potential treatment for schizophrenia via astrocytic and neuroimmune modulation.

Background: The reduced life expectancy observed in individuals with schizophrenia (SCZ) underscores the urgent need for novel therapeutic targets. Emerging evidence suggests that astrocytic dysfunction and immune-inflammatory processes contribute to SCZ pathophysiology. Low-dose methotrexate (MTX), an established immunomodulatory drug used for non-neurological conditions, demonstrated antipsychotic potential in early SCZ.

The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1CD8 T cells.

During persistent antigen stimulation, CD8 T cell responses are maintained by progenitor exhausted CD8 T (Tpex) cells. Tpex cells respond to blockade of the inhibitory receptor programmed cell death-1 (PD-1), and regulation of their differentiation is critical for immunotherapies. Tpex cells highly express inducible costimulator (ICOS), but how ICOS modulates PD-1CD8 T cells is not clear.

Activation of the IDO1-GCN2-ATF4-CHOP Pathway During the Massive Generation of Antibody-Secreting Cells in Dengue Patients Through Single-Cell Transcriptomics.

Dengue, a widespread mosquito-borne disease, annually afflicts millions globally, posing substantial mortality risks. Preceding disease defervescence, a marked and transient surge in antibody-secreting cell (ASC) frequency correlates with disease severity, paralleled by heightened tryptophan degradation. Investigating details of this process through single-cell transcriptomics from public repositories, our data pinpoint CD14+ monocytes as principal IDO1 and IDO2 expressors, implicating them, rather than B cells, in initiating tryptophan metabolism.

COVID-19 vaccination atlas using an integrative systems vaccinology approach.

The COVID-19 vaccinations have played a significant role in controlling the pandemic. To elucidate their impact on the immune system, a COVID-19 vaccination atlas was developed using an integrative systems vaccinology approach. The atlas includes 562 samples from 245 participants, including both healthy individuals and those infected with or without prior vaccination, and covers the administration of five vaccines in different regimens.

Single-cell immune profiling at time of exposure reveals antigen-reactive programs that predict progression to active disease.

Early delineation of host immune responses at the moment of (Mtb) exposure and infection is critical to identify individuals at risk of progressing to active tuberculosis (TB). We performed single-cell transcriptional profiling of over 500,000 peripheral blood mononuclear cells from 57 HIV-negative close contacts of TB cases in Brazil, including 25 individuals who developed active disease within two years (progressors) and 32 matched controls who remained disease-free (non-progressors). Cells were stimulated separately with the MTB300 peptide pool or irradiated Mtb (gRV), enabling resolution of antigen-reactive states across adaptive (CD4⁺ T-cells expressing abundant cytokines including IFNG, TNF, and IL17F) and trained-innate lineages, such as NK cells (producing GM-CSF, IFNG, CCL3, CCL4) and monocytes (GM-CSF, IL12B, IL36G).

Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis.

Introduction: Uveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.

Gene regulatory networks analysis for the discovery of prognostic genes in gliomas.

Gliomas are the most common and aggressive primary tumors of the central nervous system. Dysregulated transcription factors (TFs) and genes have been implicated in glioma progression, yet these tumors' overall structure of gene regulatory networks (GRNs) remains undefined. We analyzed transcriptional data from 989 primary gliomas in The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) to address this.

Genome-wide association study in Brazil identifies genetic susceptibility to tuberculosis with single-cell gene expression effects.

Unlabelled: Although genetic factors contribute to tuberculosis (TB) risk, no cross-population causal variants have been identified by genome-wide association studies (GWAS). Here, we utilized low-pass whole genome sequencing (lpWGS) with imputation plus detailed epidemiologic risk factors and single-cell expression quantitative loci (sceQTL) to address prior GWAS limitations. Using 947 pulmonary tuberculosis (PTB) cases and 1807 close contact controls in the Regional Prospective Observational Research in TB (RePORT) study in Brazil, we estimated PTB heritability to be 47.

Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis.

() infections range from asymptomatic (AS) to severe visceral leishmaniasis (VL). One of the manifestations is an atypical non-ulcerated cutaneous leishmaniasis (NUCL), which occurs in some locations of Central America with few cases of VL. We conducted a transcriptomic analysis of cell-mediated immunity (CMI) on blood samples from NUCL, AS, VL patients from Amapala, Honduras, and healthy controls.

Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease.

Chikungunya virus (CHIKV) infection often results in a chronic joint condition known as Post-Chikungunya Chronic Inflammatory Joint Disease (pCHIKV-CIJD). This condition disrupts individuals' daily lives and contributes to increased healthcare expenditure. This study investigated the molecular mechanisms underlying pCHIKV-CIJD development by analyzing RNA transcripts, including small RNAs, of whole blood from CHIKV-infected patients.

Revealing shared molecular drivers of brain metastases from distinct primary tumors.

Brain metastasis is the most common type of brain cancer, associated with significant neurological dysfunction and a poor prognosis. We investigated the transcriptome of 128,421 single-cells of 36 brain metastases, originating from a variety of primary tumors, including melanoma, breast, lung, ovarian, colorectal, and renal cancers. Our aim was to identify common molecular factors across these tumors, shedding light on key interactions that facilitate tumor establishment in the brain.

System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.

We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.

Prion protein regulates invasiveness in glioblastoma stem cells.

Background: Glioblastoma (GBM) is an aggressive brain tumor driven by glioblastoma stem cells (GSCs), which represent an appealing target for therapeutic interventions. The cellular prion protein (PrP), a scaffold protein involved in diverse cellular processes, interacts with various membrane and extracellular matrix molecules, influencing tumor biology. Herein, we investigate the impact of PrP expression on GBM.

Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients.

In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients.

Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility.

Thyroid autoimmune diseases, such as Hashimoto thyroiditis and Graves disease, are significantly more prevalent in women than in men, suggesting underlying biological differences in immune system function and regulation between sexes. Plasma B cells are crucial in autoimmunity due to their role in producing antibodies targeting self-antigens, but their presence in the thyroids of women without clinical autoimmune diseases remains largely unexplored. This study investigates the infiltration of plasma B cells in female thyroids specifically excluding those with any clinical signs of autoimmune diseases.

The single-cell transcriptome of mTECs and CD4 thymocytes under adhesion revealed heterogeneity of mTECs and a network controlled by and lncRNAs.

To further understand the impact of deficiency of the autoimmune regulator () gene during the adhesion of medullary thymic epithelial cells (mTECs) to thymocytes, we sequenced single-cell libraries (scRNA-seq) obtained from wild-type (WT) ( ) or -deficient ( ) mTECs cocultured with WT single-positive (SP) CD4 thymocytes. Although the libraries differed in their mRNA and long noncoding RNA (lncRNA) profiles, indicating that mTECs were heterogeneous in terms of their transcriptome, UMAP clustering revealed that both mTEC lines expressed their specific markers, i.e.

Chikungunya-Driven Gene Expression Linked to Osteoclast Survival and Chronic Arthralgia.

Chikungunya fever (CHIKF), caused by the Chikungunya virus (CHIKV), manifests as acute febrile illness often associated with polyarthritis and polyarthralgia. Although the acute symptoms resolve within two weeks, many patients experience prolonged joint pain and inflammation, resembling rheumatoid arthritis (RA). This study aimed to identify molecular markers related to joint pain and chronicity in CHIKV-infected individuals by analyzing blood transcriptomes using bulk RNA sequencing.

The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review.

Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024.

Replication, safety and immunogenicity of the vectored Ebola vaccine rVSV-ΔG-ZEBOV-GP in a sub-Saharan African paediatric population: A randomised controlled, open-label trial in children aged 1-12 years living in Lambaréné, Gabon.

Background: Unlike adults, children experienced stronger and longer vector replication in plasma and shedding in saliva following rVSVΔG-ZEBOV-GP vaccination. The resulting risks of immunosuppression or immune hyperactivation leading to increased Adverse Events (AEs) and altered antibody responses are concerns that have been addressed in the present manuscript.

Methods: Children aged 1-12 years living in Gabon received either rVSVΔG-ZEBOV-GP (ERVEBO®) vaccine or the varicella-zoster virus (VZV) vaccine (VZV).

Poly I:C elicits broader and stronger humoral and cellular responses to a circumsporozoite protein malaria vaccine than Alhydrogel in mice.

Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C.