Transcriptional profile of human thymus reveals IGFBP5 is correlated with age-related thymic involution.

Thymus is the main immune organ which is responsible for the production of self-tolerant and functional T cells, but it shrinks rapidly with age after birth. Although studies have researched thymus development and involution in mouse, the critical regulators that arise with age in human thymus remain unclear. We collected public human single-cell transcriptomic sequencing (scRNA-seq) datasets containing 350,678 cells from 36 samples, integrated them as a cell atlas of human thymus.

Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis.

Male infertility is a global health problem especially prevalent in high-altitude regions. The epididymis is essential for sperm maturation, but the influence of environmental cues on its reshaping remains poorly understood. Here, we use single-cell transcriptomics to track the cellular profiles of epidydimal cells in rats raised under normoxia or extended hypoxia.

A positive-feedback loop between HBx and ALKBH5 promotes hepatocellular carcinogenesis.

Background: Hepatitis B Virus (HBV) contributes to liver carcinogenesis via various epigenetic mechanisms. The newly defined epigenetics, epitranscriptomics regulation, has been reported to involve in multiple cancers including Hepatocellular Carcinoma (HCC). Our previous study found that HBx, HBV encodes X protein, mediated H3K4me3 modification in WDR5-dependent manner to involve in HBV infection and contribute to oncogene expression.

Profiling single-cell histone modifications using indexing chromatin immunocleavage sequencing.

Recently, multiple single-cell assays were developed for detecting histone marks at the single-cell level. These techniques are either limited by the low cell throughput or sparse reads which limit their applications. To address these problems, we introduce indexing single-cell immunocleavage sequencing (iscChIC-seq), a multiplex indexing method based on TdT terminal transferase and T4 DNA ligase-mediated barcoding strategy and single-cell ChIC-seq, which is capable of readily analyzing histone modifications across tens of thousands of single cells in one experiment.

Multiplex indexing approach for the detection of DNase I hypersensitive sites in single cells.

Single cell chromatin accessibility assays reveal epigenomic variability at cis-regulatory elements among individual cells. We previously developed a single-cell DNase-seq assay (scDNase-seq) to profile accessible chromatin in a limited number of single cells. Here, we report a novel indexing strategy to resolve single-cell DNase hypersensitivity profiles based on bulk cell analysis.

C5a/C5aR1 mediates IMQ-induced psoriasiform skin inflammation by promoting IL-17A production from γδ-T cells.

Psoriasis is a chronic relapsing inflammatory skin disease, affecting up to 3% of the global population. Accumulating evidence suggests that the complement system is involved in its pathogenesis. Our previous study revealed that the C5a/C5aR1 pathway is crucial for disease development.

Genome-wide profiling of nucleosome position and chromatin accessibility in single cells using scMNase-seq.

Nucleosome organization is important for chromatin compaction and accessibility. Profiling nucleosome positioning genome-wide in single cells provides critical information to understand the cell-to-cell heterogeneity of chromatin states within a cell population. This protocol describes single-cell micrococcal nuclease sequencing (scMNase-seq), a method for detecting genome-wide nucleosome positioning and chromatin accessibility simultaneously from a small number of cells or single cells.

HBx Protein Contributes to Liver Carcinogenesis by H3K4me3 Modification Through Stabilizing WD Repeat Domain 5 Protein.

Background And Aims: Cancer is typically considered as a genetic and epigenetic disease. Although numerous studies have indicated that an aberrant structure, function, or expression level of epigenetic enzymes contribute to many tumor types, precisely how the epigenetic mechanisms are involved in the hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) remains unknown.

Approach And Results: In this study, we found that the WD repeat domain 5 protein (WDR5)-a core subunit of histone H3 lysine 4 methyltransferase complexes, which catalyze the generation of histone H3 lysine 4 trimethylation (H3K4me3) modification-is highly expressed in HBV-related HCC and promotes HCC development.

Single-cell chromatin immunocleavage sequencing (scChIC-seq) to profile histone modification.

Our method for analyzing histone modifications, scChIC-seq (single-cell chromatin immunocleavage sequencing), involves targeting of the micrococcal nuclease (MNase) to a histone mark of choice by tethering to a specific antibody. Cleaved target sites are then selectively PCR amplified. We show that scChIC-seq reliably detects H3K4me3 and H3K27me3 target sites in single human white blood cells.

Circular RNA expression profiles of peripheral blood mononuclear cells in hepatocellular carcinoma patients by sequence analysis.

Circular RNAs (circRNAs) are a large class of noncoding RNAs that have potential regulatory roles in disease pathogenesis and progression. Recently, circRNAs have been found to be expressed in hepatocellular carcinoma (HCC) tissues and involved in the development and metastasis of HCC. However, the significance of circRNAs in peripheral blood mononuclear cells (PBMCs) of HCC patients remains unclear.

Prognostic Values of CD38CD101PD1CD8 T Cells in Pancreatic Cancer.

Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1 T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy.

Publisher Correction: Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing.

Change history: In Fig. 1c of this Letter, the two graphs were duplicates. The right panel of Fig.

Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing.

Nucleosome positioning is critical to chromatin accessibility and is associated with gene expression programs in cells. Previous nucleosome mapping methods assemble profiles from cell populations and reveal a cell-averaged pattern: nucleosomes are positioned and form a phased array that surrounds the transcription start sites of active genes and DNase I hypersensitive sites. However, even in a homogenous population of cells, cells exhibit heterogeneity in expression in response to active signalling that may be related to heterogeneity in chromatin accessibility.

Diverse effects of interleukin-22 on pancreatic diseases.

Interleukin-22 (IL-22) is involved in the development of lymphocytes and serves as a rapid and early source of the effector cytokines that are released in response to pathogen-induced changes in the microenvironment. Recent research has implicated IL-22 as a potential contributing factor to the spectrum of inflammation-related pancreatic diseases, particularly pancreatitis, fibrosis, carcinoma and diabetes. In this review, we summarize the current knowledge on the roles of IL-22 in the various pancreatic pathogenesis, providing insights into the underlying cellular and signaling mechanisms that will help guide future research into promising interventional targets with therapeutic potential.

Dual roles of IL-22 at ischemia-reperfusion injury and acute rejection stages of rat allograft liver transplantation.

Interleukin-22 (IL-22) is a recently identified regulator of inflammation, but little is known about its role in liver transplantation. Therefore, in this study, we explored the roles and the underlying mechanisms of IL-22 in acute allograft rejection by using a rat allogeneic liver transplantation model. Results showed that allograft liver transplantation led to damage of the parent liver and to significantly increased IL-22 expression in the allograft liver and plasma of the recipient rats compared with the rats who received isografts.

Critical effects of long non-coding RNA on fibrosis diseases.

The expression or dysfunction of long non-coding RNAs (lncRNAs) is closely related to various hereditary diseases, autoimmune diseases, metabolic diseases and tumors. LncRNAs were also recently recognized as functional regulators of fibrosis, which is a secondary process in many of these diseases and a primary pathology in fibrosis diseases. We review the latest findings on lncRNAs in fibrosis diseases of the liver, myocardium, kidney, lung and peritoneum.

Multifunctional YY1 in Liver Diseases.

The transcription factor Yin Yang 1 (YY1) is a multifunctional protein that can activate or repress gene expression, depending on the cellular context. While YY1 is ubiquitously expressed and highly conserved between species, its role varies among the diverse cell types and includes proliferation, differentiation, and apoptosis. Upregulated YY1 expression is found in pathogenic conditions, such as human hepatocellular carcinoma and hepatitis B virus infection, and its roles in the molecular pathogenic mechanisms in liver (i.

Histone Deacetylase 1 Regulates the Expression of Progesterone Receptor A During Human Parturition by Occupying the Progesterone Receptor A Promoter.

The functional withdrawal of progesterone is mediated by the enhanced expression ratio of the 2 progesterone receptor (PR) isoforms, PRA and PRB, and causes the pregnant human myometrium to switch from a quiet state to a state of excitation-contraction and subsequent laboring. However, the precise mechanisms responsible for alterations in PRA and PRB expression during human parturition have yet to be resolved. In the present study, we report that PRA expression was increased in myometrium samples during labor (P < .

Role of Ets Proteins in Development, Differentiation, and Function of T-Cell Subsets.

Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes.

Mutual interaction between BCL6 and microRNAs in T cell differentiation.

The transcription factor B-cell CLL/lymphoma 6 (BCL6) and the regulatory factor microRNAs (miRNAs) are of great importance in the differentiation of T cell subsets. An increasing body of evidence has demonstrated that BCL6 and miRNAs can target one another and mutually adjust their expression in T cell subsets, such as T helper (Th)-2, Th17, CD8+ regulatory T (CD8+Treg) and T follicular helper (Tfh) cells. Here, we discuss the most recent advances and emerging concepts in how BCL6 and miRNAs regulate one another, and the effects of such mutual regulations on T cell subset differentiation.

Yin-Yang Regulation of RORγt Protein Complex in Th17 Differentiation.

T helper 17 (Th17) cells have been identified as a distinct T helper lineage that mediates tissue inflammation. Retinoic acid receptor-related orphan receptor (ROR) γt has been identified as the master transcription factor (TF) required for Th17 cell lineage commitment. There is an established consensus that TFs never function alone.