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 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 Events at the transition between cell cycle exit and oligodendrocyte progenitor differentiation: the role of HDAC and YY1

2007 ◽  
Vol 3 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Ye He ◽  
Juan Sandoval ◽  
Patrizia Casaccia-Bonnefil
Keyword(s):  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Histone Deacetylation ◽  
Adult Brain ◽  
Oligodendrocyte Differentiation ◽  
Transcriptional Regulatory Networks ◽  
Histone Deacetylase 1 ◽  
Transcriptional Regulatory ◽  
Functional Consequences

AbstractThe complexity of the adult brain is the result of an integrated series of developmental events that depends on appropriate timing of differentiation. The importance of transcriptional regulatory networks and epigenetic mechanisms of regulation of gene expression is becoming increasingly evident. Among these mechanisms, previous work has revealed the importance of histone deacetylation in oligodendrocyte differentiation. In this manuscript we define the region of interaction between transcription factor Yin-Yang 1 (YY1) and histone deacetylase 1, and characterize the functional consequences of YY1 overexpression on the differentiation of oligodendrocyte progenitors.

scholarly journals Role of SARS-CoV-2 in Altering the RNA-Binding Protein and miRNA-Directed Post-Transcriptional Regulatory Networks in Humans

2020 ◽  
Vol 21 (19) ◽  
pp. 7090
Author(s):  
Rajneesh Srivastava ◽  
Swapna Vidhur Daulatabad ◽  
Mansi Srivastava ◽  
Sarath Chandra Janga
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Immune Cells ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Human Tissues ◽  
Transcriptional Regulatory Networks ◽  
Differential Outcomes ◽  
Transcriptional Regulatory

The outbreak of a novel coronavirus SARS-CoV-2 responsible for the COVID-19 pandemic has caused a worldwide public health emergency. Due to the constantly evolving nature of the coronaviruses, SARS-CoV-2-mediated alterations on post-transcriptional gene regulations across human tissues remain elusive. In this study, we analyzed publicly available genomic datasets to systematically dissect the crosstalk and dysregulation of the human post-transcriptional regulatory networks governed by RNA-binding proteins (RBPs) and micro-RNAs (miRs) due to SARS-CoV-2 infection. We uncovered that 13 out of 29 SARS-CoV-2-encoded proteins directly interacted with 51 human RBPs, of which the majority of them were abundantly expressed in gonadal tissues and immune cells. We further performed a functional analysis of differentially expressed genes in mock-treated versus SARS-CoV-2-infected lung cells that revealed enrichment for the immune response, cytokine-mediated signaling, and metabolism-associated genes. This study also characterized the alternative splicing events in SARS-CoV-2-infected cells compared to the control, demonstrating that skipped exons and mutually exclusive exons were the most abundant events that potentially contributed to differential outcomes in response to the viral infection. A motif enrichment analysis on the RNA genomic sequence of SARS-CoV-2 clearly revealed the enrichment for RBPs such as SRSFs, PCBPs, ELAVs, and HNRNPs, suggesting the sponging of RBPs by the SARS-CoV-2 genome. A similar analysis to study the interactions of miRs with SARS-CoV-2 revealed functionally important miRs that were highly expressed in immune cells, suggesting that these interactions may contribute to the progression of the viral infection and modulate the host immune response across other human tissues. Given the need to understand the interactions of SARS-CoV-2 with key post-transcriptional regulators in the human genome, this study provided a systematic computational analysis to dissect the role of dysregulated post-transcriptional regulatory networks controlled by RBPs and miRs across tissue types during a SARS-CoV-2 infection.

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 Zic3 Is Required for Maintenance of Pluripotency in Embryonic Stem Cells

2007 ◽  
Vol 18 (4) ◽  
pp. 1348-1358 ◽  
Author(s):  
Linda Shushan Lim ◽  
Yuin-Han Loh ◽  
Weiwei Zhang ◽  
Yixun Li ◽  
Xi Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Embryonic Stem ◽  
Es Cell ◽  
Lineage Specification ◽  
Mouse Es Cells

Embryonic stem (ES) cell pluripotency is dependent upon sustained expression of the key transcriptional regulators Oct4, Nanog, and Sox2. Dissection of the regulatory networks downstream of these transcription factors has provided critical insight into the molecular mechanisms that regulate ES cell pluripotency and early differentiation. Here we describe a role for Zic3, a member of the Gli family of zinc finger transcription factors, in the maintenance of pluripotency in ES cells. We show that Zic3 is expressed in ES cells and that this expression is repressed upon differentiation. The expression of Zic3 in pluripotent ES cells is also directly regulated by Oct4, Sox2, and Nanog. Targeted repression of Zic3 in human and mouse ES cells by RNA interference–induced expression of several markers of the endodermal lineage. Notably, the expression of Nanog, a key pluripotency regulator and repressor of extraembryonic endoderm specification in ES cells, was significantly reduced in Zic3 knockdown cells. This suggests that Zic3 may prevent endodermal marker expression through Nanog-regulated pathways. Thus our results extend the ES cell transcriptional network beyond Oct4, Nanog, and Sox2, and further establish that Zic3 plays an important role in the maintenance of pluripotency by preventing endodermal lineage specification in embryonic stem cells.

scholarly journals Rfx6 promotes the differentiation of peptide-secreting enteroendocrine cells while repressing genetic programs controlling serotonin production

2019 ◽  
Author(s):  
Julie Piccand ◽  
Constance Vagne ◽  
Florence Blot ◽  
Aline Meunier ◽  
Anthony Beucher ◽  
...  
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Neonatal Diabetes ◽  
Enteroendocrine Cells ◽  
Rna Seq ◽  
Adaptive Responses ◽  
Mouse Intestine

ABSTRACTObjectiveEnteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake and storage. Our goal is to decipher the gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied the role of the transcription factor Rfx6 which had been identified as the cause of Mitchell-Riley syndrome characterized by neonatal diabetes and congenital malabsorptive diarrhea. We previously reported that Rfx6 was essential for pancreatic beta cell development and function, however, the role of Rfx6 in EECs differentiation remained to be elucidated.MethodsWe examined the molecular, cellular and metabolic consequences of constitutive and conditional deletion of Rfx6 in the embryonic and adult mouse intestine. We performed single cell and bulk RNA-Seq to characterize EECs diversity and identify Rfx6-regulated genes.ResultsRfx6 is expressed in the gut endoderm; later it is turned on in, and restricted to, enteroendocrine progenitors and persists in hormone-positive EECs. In the embryonic intestine, the constitutive lack of Rfx6 leads to gastric heterotopia, suggesting a role in the maintenance of intestinal identity. In the absence of intestinal Rfx6, EECs differentiation is severely impaired both in the embryo and adult. However, the number of serotonin-producing enterochromaffin cells and mucosal 5-HT content are increased. Concomitantly, Neurog3-positive enteroendocrine progenitors accumulate. Combined analysis of single-cell and bulk RNA-Seq data revealed that enteroendocrine progenitors differentiate in two main cell trajectories, the enterochromaffin (EC) cells and the Peptidergic Enteroendocrine (PE) cells, whose differentiation programs are differentially regulated by Rfx6. Rfx6 operates upstream of Arx, Pax6 and Isl1 to trigger the differentiation of peptidergic EECs such as GIP-, GLP-1- or CCK-secreting cells. On the contrary, Rfx6 represses Lmx1a and Tph1, two genes essential for serotonin biosynthesis. Finally, we identified transcriptional changes uncovering adaptive responses to the prolonged lack of enteroendocrine hormones and leading to malabsorption and lower food efficiency ratio in Rfx6-deficient mouse intestine.ConclusionThese studies identify Rfx6 as an essential transcriptional regulator of EECs specification and shed light on the molecular mechanisms of intestinal failures in human RFX6-deficiencies such as Mitchell-Riley syndrome.

scholarly journals Role of SARS-CoV-2 in altering the RNA binding protein and miRNA directed post-transcriptional regulatory networks in humans

2020 ◽  
Author(s):  
Rajneesh Srivastava ◽  
Swapna Vidhur Daulatabad ◽  
Mansi Srivastava ◽  
Sarath Chandra Janga
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Immune Cells ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Human Tissues ◽  
Transcriptional Regulatory Networks ◽  
Differential Outcomes ◽  
Transcriptional Regulatory

AbstractThe outbreak of a novel coronavirus SARS-CoV-2 responsible for COVID-19 pandemic has caused worldwide public health emergency. Due to the constantly evolving nature of the coronaviruses, SARS-CoV-2 mediated alteration on post-transcriptional gene regulation across human tissues remains elusive. In this study, we analyze publicly available genomic datasets to systematically dissect the crosstalk and dysregulation of human post-transcriptional regulatory networks governed by RNA binding proteins (RBPs) and micro-RNAs (miRs), due to SARS-CoV-2 infection. We uncovered that 13 out of 29 SARS-CoV-2 encoded proteins directly interact with 51 human RBPs of which majority of them were abundantly expressed in gonadal tissues and immune cells. We further performed a functional analysis of differentially expressed genes in mock-treated versus SARS-CoV-2 infected lung cells that revealed enrichment for immune response, cytokine-mediated signaling, and metabolism associated genes. This study also characterized the alternative splicing events in SARS-CoV-2 infected cells compared to control demonstrating that skipped exons and mutually exclusive exons were the most abundant events that potentially contributed to differential outcomes in response to viral infection. Motif enrichment analysis on the RNA genomic sequence of SARS-CoV-2 clearly revealed the enrichment for RBPs such as SRSFs, PCBPs, ELAVs, and HNRNPs suggesting the sponging of RBPs by SARS-CoV-2 genome. A similar analysis to study the interactions of miRs with SARS-CoV-2 revealed functionally important miRs that were highly expressed in immune cells, suggesting that these interactions may contribute to the progression of the viral infection and modulate host immune response across other human tissues. Given the need to understand the interactions of SARS-CoV-2 with key post-transcriptional regulators in the human genome, this study provides a systematic computational analysis to dissect the role of dysregulated post-transcriptional regulatory networks controlled by RBPs and miRs, across tissues types during SARS-CoV-2 infection.

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.

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