scholarly journals Effects of poor sleep on the immune cell landscape as assessed by single-cell analysis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiuxing Liu ◽  
Binyao Chen ◽  
Zhaohao Huang ◽  
Runping Duan ◽  
He Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Tumor Development ◽  
Public Health Issue ◽  
Poor Sleep ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory

AbstractPoor sleep has become an important public health issue. With loss of sleep durations, poor sleep has been linked to the increased risks for diseases. Here we employed mass cytometry and single-cell RNA sequencing to obtain a comprehensive human immune cells landscape in the context of poor sleep, which was analyzed in the context of subset composition, gene signatures, enriched pathways, transcriptional regulatory networks, and intercellular interactions. Participants subjected to staying up had increased T and plasma cell frequency, along with upregulated autoimmune-related markers and pathways in CD4+ T and B cells. Additionally, staying up reduced the differentiation and immune activity of cytotoxic cells, indicative of a predisposition to infection and tumor development. Finally, staying up influenced myeloid subsets distribution and induced inflammation development and cellular senescence. These findings could potentially give high-dimensional and advanced insights for understanding the cellular and molecular mechanisms of pathologic conditions related to poor sleep.

scholarly journals Identification of KLF6/PSGs and NPY-Related USF2/CEACAM Transcriptional Regulatory Networks via Spinal Cord Bulk and Single-Cell RNA-Seq Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Xinbing Liu ◽  
Wei Gao ◽  
Wei Liu
Keyword(s):  
Spinal Cord ◽  
Single Cell ◽  
Regulatory Networks ◽  
Single Cell Analysis ◽  
Transcriptional Regulatory Network ◽  
Transcriptional Regulator ◽  
Cell Analysis ◽  
Rna Seq ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory

Background. To further understand the development of the spinal cord, an exploration of the patterns and transcriptional features of spinal cord development in newborn mice at the cellular transcriptome level was carried out. Methods. The mouse single-cell sequencing (scRNA-seq) dataset was downloaded from the GSE108788 dataset. Single-cell RNA-Seq (scRNA-Seq) was conducted on cervical and lumbar spinal V2a interneurons from 2 P0 neonates. Single-cell analysis using the Seurat package was completed, and marker mRNAs were identified for each cluster. Then, pseudotemporal analysis was used to analyze the transcription changes of marker mRNAs in different clusters over time. Finally, the functions of these marker mRNAs were assessed by enrichment analysis and protein-protein interaction (PPI) networks. A transcriptional regulatory network was then constructed using the TRRUST dataset. Results. A total of 949 cells were screened. Single-cell analysis was conducted based on marker mRNAs of each cluster, which revealed the heterogeneity of neonatal mouse spinal cord neuronal cells. Functional analysis of pseudotemporal trajectory-related marker mRNAs suggested that pregnancy-specific glycoproteins (PSGs) and carcinoembryonic antigen cell adhesion molecules (CEACAMs) were the core mRNAs in cluster 3. GSVA analysis then demonstrated that the different clusters had differences in pathway activity. By constructing a transcriptional regulatory network, USF2 was identified to be a transcriptional regulator of CEACAM1 and CEACAM5, while KLF6 was identified to be a transcriptional regulator of PSG3 and PSG5. This conclusion was then validated using the Genotype-Tissue Expression (GTEx) spinal cord transcriptome dataset. Conclusions. This study completed an integrated analysis of a single-cell dataset with the utilization of marker mRNAs. USF2/CEACAM1&5 and KLF6/PSG3&5 transcriptional regulatory networks were identified by spinal cord single-cell analysis.

scholarly journals Single Cell Pluripotency Regulatory Networks

2016 ◽  
Author(s):  
Patrick S. Stumpf ◽  
Rob Ewing ◽  
Ben D. MacArthur
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Embryonic Stem ◽  
Transcriptional Regulatory Networks ◽  
Cell Behaviour ◽  
Transcriptional Regulatory ◽  
Spatiotemporal Integration

AbstractEmbryonic stem (ES) cells represent a popular model system for investigating development, tissue regeneration and repair. Although much is known about the molecular mechanisms that regulate the balance between self-renewal and lineage commitment in ES cells, the spatiotemporal integration of responsive signalling pathways with core transcriptional regulatory networks are complex and only partially understood. Moreover, measurements made on populations of cells reveal only average properties of the underlying regulatory networks, obscuring their fine detail. Here, we discuss the reconstruction of regulatory networks in individual cells using novel single cell transcriptomics and proteomics, in order to expand our understanding of the molecular basis of pluripotency, including the role of cell-cell variability within ES cell populations, and ways in which networks may be controlled in order to reliably manipulate cell behaviour.

scholarly journals Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

2021 ◽  
Author(s):  
Zhibin Li ◽  
chengcheng Sun ◽  
Fei Wang ◽  
Xiran Wang ◽  
Jiacheng Zhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Evolutionary Biology ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetic Regulatory Networks ◽  
Peripheral Blood Mononuclear

Background: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods: In this study, we compared the single-cell transcriptomes of 77 957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results: The results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular cross-talks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. Conclusions: This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders

scholarly journals Putative regulators for the continuum of erythroid differentiation revealed by single-cell transcriptome of human BM and UCB cells

2020 ◽  
Vol 117 (23) ◽  
pp. 12868-12876 ◽  
Author(s):  
Peng Huang ◽  
Yongzhong Zhao ◽  
Jianmei Zhong ◽  
Xinhua Zhang ◽  
Qifa Liu ◽  
...  
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Erythroid Differentiation ◽  
Transcriptional Regulatory Networks ◽  
Hematopoietic Stem ◽  
Delayed Differentiation ◽  
Transcriptional Regulatory ◽  
Cell Transcriptome ◽  
Fine Resolution ◽  
Terminal Erythroid Differentiation

Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34−CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes,AKAP8L,TERF2IP, andRNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown ofAKAP8Lsuppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown ofTERF2IPandRNF10delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.

scholarly journals Cellular and Molecular Specificity of Pituitary Gland Physiology

2012 ◽  
Vol 92 (1) ◽  
pp. 1-38 ◽  
Author(s):  
Carolina Perez-Castro ◽  
Ulrich Renner ◽  
Mariana R. Haedo ◽  
Gunter K. Stalla ◽  
Eduardo Arzt
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Regulatory System ◽  
Anterior Pituitary Gland ◽  
Complex Signals ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

scholarly journals Transcriptional regulatory networks mediated by abnormal m6A modifications in tumor development

2021 ◽  
Author(s):  
Wenzheng Qu ◽  
Xuekun Li
Keyword(s):  
Regulatory Networks ◽  
Tumor Development ◽  
Mapk Signaling ◽  
Rna Seq ◽  
Sequencing Data ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
The Common ◽  
Related Proteins ◽  
Geo Database

Abstract Background N6-methyladenosine (m6A) is one of the common modifications of transcripts that is regulated by related proteins including writers, readers and erasers. Abnormal m6A modification plays an important role in the process of tumor development. Current approaches for tumor m6A RNA methylation, based on sequencing data from public databases, focus on the comparison of m6A modification regulator expression by RNA-seq data. Results We obtained MeRIP-seq and corresponding RNA-seq data from GEO database to compare and analyze the distributional characteristics of m6A in different types of tumor samples, the differences in m6A modification enrichment, and the regulatory role in gene transcriptional expression level. We found that the enrichment of m6A modification was enhanced in IMPA and GBM tumor samples, but was decreased in METTL3 knockdown tumor cells. Combined with clinical data from the TCGA database, we found that the high expression of DUSP7 significantly affected the overall survival of AML patients and was involved in tumor development through the PIK3R2 protein and MAPK signaling pathways. Conclusion Abnormal m6A modification enrichment in tumor samples leads to dysregulation in the expression of cancer-related genes.

Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

2021 ◽  
Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Progesterone Receptors ◽  
Activator Protein 1 ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Pathways ◽  
Transcriptional Regulatory ◽  
Mechanistic Basis ◽  
Labour Onset

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

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