ABSTRACT
Single-cell multimodal sequencing parallelly captures multiple modalities of the same cell, providing unparalleled insights into cell heterogeneity and cell dynamics. For example, joint profiling of chromatin accessibility and transcriptome from the same single cell (scATAC + RNA) identified new cell subsets within the well-defined clusters. However, lack of single-cell multimodal omics (scMMO) database has led to data fragmentation, seriously hindering access, utilization and mining of scMMO data. Here, we constructed a scMMO atlas by collecting and integrating various scMMO data, then constructed scMMO database and portal called scMMO-atlas (https://www.biosino.org/scMMO-atlas/). scMMO-atlas includes scATAC + RNA (ISSAAS-seq, SNARE-seq, paired-seq, sci-CAR, scCARE-seq, 10X Multiome and so on), scRNA + protein, scATAC + protein and scTri-modal omics data, with 3 168 824 cells from 27 cell tissues/organs. scMMO-atlas offered an interactive portal for visualization and featured analysis for each modality and the integrated data. Integrated analysis of scATAC + RNA data of mouse cerebral cortex in scMMO-atlas identified more cell subsets compared with unimodal omics data. Among these new cell subsets, there is an early astrocyte subset highly expressed Grm3, called Astro-Grm3. Furthermore, we identified Ex-L6-Tle4-Nrf1, a progenitor of Ex-L6-Tle4, indicating the statistical power provided by the big data in scMMO-atlas. In summary, scMMO-atlas offers cell atlas, database and portal to facilitate data utilization and biological insight.
ABSTRACT
T cell activation is a key event in adaptive immunity. However, the dynamics and influencing factors of T cell activation remain unclear. Here, we analyzed CD4 T cells that were stimulated with anti-CD3/CD28 under several conditions to explore the factors affecting T cell activation. We found a stimulated T subset (HSPhi T) highly expressing heat shock proteins, which was derived from stimulated naive T. We identified and characterized inert T, a stimulated T cell subset in transitional state from resting T to activated T. Interestingly, resting CXCR4low T responded to stimulation more efficiently than resting CXCR4hi T. Furthermore, stimulation of CD4 T in the presence of CD8 T resulted in more effector T and more homogeneous expressions of CD25, supporting that presence of CD8 T reduces the extreme response of T cells, which can be explained by regulation of CD4 T activation through CD8 T-initiated cytokine signaling and FAS/FASLG signaling.
ABSTRACT
Multiple mental diseases could arise in people who have the disrupted in schizophrenia 1 (DISC1) gene. However, it was unknown how DISC1 might contribute to the development of tumors and immune responses. We extracted data from the Cancer Genome Atlas (TCGA) and TISIDB databases from stomach adenocarcinoma (STAD) patients, which revealed that DISC1 overexpression was closely associated with tumor histological type (mucinous vs. tubular, OR = 2.860, CI = 1.423-5.872, p = 0.004), as well as tumor stage and grade. Furthermore, the higher the DISC1 expression, the lower the overall 10-year survival rate. Patients with low DISC1 expression had a significantly longer progression-free interval (PFI) and disease-specific survival (DSS) than patients with high DISC1 expression. However, patients with higher DISC1 expression in the T3&T4, N0&N1 and M0 subgroups had poorer prognosis in terms of OS, DSS and PFI, as could be seen in the subgroup survival analysis. Public datasets were used to predict lncRNA-miRNA-DISC1 regulation. DISC1 was significantly up-regulated in GC(gastric cancer), and its expression levels showed a moderate to strong positive correlation with infiltration levels of effector memory T cells (Tem) and central memory T cells (Tcm), and a negative correlation was observed with Th17 cells and NK CD56bright cells. In addition, concomitant with the high expression of the DISC1 gene was a decrease in MHC-I (Major Histocompatibility Complex-I)expression and an increase in MHC-II expression, and altered chemokine expression. The upregulation of CXCL12 and CXCR4 expression could be caused by an increase in DISC1 expression. The above expression variability and correlation suggest a role for DISC1 in regulating tumor immunity in GC. These findings suggest that high expression of DISC1 could be an independent prognostic factor for GC.
ABSTRACT
Social frailty is a geriatric public health problem that deeply affects healthy aging. Currently, evidence on the prevalence and factors associated with social frailty in older adults remains unclear. Our study aims to estimate the prevalence and related factors of social frailty in older adults. This study retrieved nine electronic databases searched through July 5th, 2022. The prevalence of social frailty was pooled using Stata software. It was found that older adults suffered from a "moderate" level of social frailty. We found a higher prevalence of social frailty in the United Kingdom, Greece, Croatia, The Netherlands, and Spain, in people over 75 years, in hospitals, and during the Coronavirus Disease 2019 (COVID-19). We believed that countries, age, research sites, and the pandemic of COVID-19 were influencing factors of social frailty among older adults. These findings may provide a theoretical basis for the development of ameliorating social frailty among older adults.