Transcriptome Analysis of Umbilical Cord Mesenchymal Stem Cells Revealed Fetal Programming Due to Chorioamnionitis

Abstract Although chorioamnionitis (CAM) has been demonstrated to be associated with numerous short- and long-term morbidities, the precise mechanisms remain unclear. One of the reasons for this is the lack of appropriate models for analyzing the relationship between the fetal environment and chorioamnionitis and fetal programming in humans. In this study, we aimed to clarify the fetal programming caused by CAM using the gene expression profiles of UCMSCs.. From nine preterm neonates with CAM (n=4) or without CAM (n=5), we established UCMSCs.The gene expression profiles obtained by RNA-seq analysis revealed distinctive changes in the CAM group USMSCs. The UCMSCs in the CAM group had a myofibroblast-like phenotype with significantly increased expression levels of myofibroblast-related genes, including α-smooth muscle actin (p<0.05). In the pathway analysis, the genes involved in DNA replication and G1 to S cell cycle control were remarkably decreased, suggesting that cellular proliferation was impaired, as confirmed by the cellular proliferation assay (p<0.01 ~ 0.05). Pathway analysis revealed that genes related to white fat cell differentiation were significantly increased. Our results could explain the long-term outcomes of patients who were exposed to CAM and revealed that UCMSCs could be an in vitro model of fetal programming affected by CAM.

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Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

10.22541/au.160655409.95797246/v1 ◽

2020 ◽

Author(s):

Zhenhua Dang ◽

Yuanyuan Jia ◽

Yunyun Tian ◽

Jiabin Li ◽

Yanan Zhang ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Pathways ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Grazing Intensity ◽

Glycolate Oxidase ◽

Bisphosphate Carboxylase ◽

Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

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Merkel Cell Polyomavirus Downregulates N-myc Downstream-Regulated Gene 1, Leading to Cellular Proliferation and Migration

Journal of Virology ◽

10.1128/jvi.00899-19 ◽

2019 ◽

Vol 94 (3) ◽

Cited By ~ 1

Author(s):

Purnima Gupta ◽

Naveed Shahzad ◽

Alexis Harold ◽

Masahiro Shuda ◽

Assunta Venuti ◽

...

Keyword(s):

Gene Expression ◽

Cell Carcinoma ◽

Cellular Proliferation ◽

Expression Profiles ◽

Gene Expression Profiles ◽

T Antigen ◽

Merkel Cell Polyomavirus ◽

Early Gene ◽

Merkel Cell ◽

Gene Expressing

ABSTRACT Merkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, viral oncogenes required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analyzed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human polyomaviruses (PyVs), including MCPyV. A comparison of the gene expression profiles revealed 28 genes specifically deregulated by MCPyV. In particular, the MCPyV early gene downregulated the expression of the tumor suppressor gene N-myc downstream-regulated gene 1 (NDRG1) in MCPyV gene-expressing NIKs and hTERT-MCPyV gene-expressing human keratinocytes (HK) compared to their expression in the controls. In MCPyV-positive MCC cells, the expression of NDRG1 was downregulated by the MCPyV early gene, as T antigen knockdown rescued the level of NDRG1. In addition, NDRG1 overexpression in hTERT-MCPyV gene-expressing HK or MCC cells resulted in a decrease in the number of cells in S phase and cell proliferation inhibition. Moreover, a decrease in wound healing capacity in hTERT-MCPyV gene-expressing HK was observed. Further analysis revealed that NDRG1 exerts its biological effect in Merkel cell lines by regulating the expression of the cyclin-dependent kinase 2 (CDK2) and cyclin D1 proteins. Overall, NDRG1 plays an important role in MCPyV-induced cellular proliferation. IMPORTANCE Merkel cell carcinoma was first described in 1972 as a neuroendocrine tumor of skin, most cases of which were reported in 2008 to be caused by a PyV named Merkel cell polyomavirus (MCPyV), the first PyV linked to human cancer. Thereafter, numerous studies have been conducted to understand the etiology of this virus-induced carcinogenesis. However, it is still a new field, and much work is needed to understand the molecular pathogenesis of MCC. In the current work, we sought to identify the host genes specifically deregulated by MCPyV, as opposed to other PyVs, in order to better understand the relevance of the genes analyzed on the biological impact and progression of the disease. These findings open newer avenues for targeted drug therapies, thereby providing hope for the management of patients suffering from this highly aggressive cancer.

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Long-term affected flat oyster (Ostrea edulis) haemocytes show differential gene expression profiles from naïve oysters in response to Bonamia ostreae

Genomics ◽

10.1016/j.ygeno.2018.04.002 ◽

2018 ◽

Vol 110 (6) ◽

pp. 390-398 ◽

Cited By ~ 5

Author(s):

P. Ronza ◽

A. Cao ◽

D. Robledo ◽

A. Gómez-Tato ◽

J.A. Álvarez-Dios ◽

...

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Ostrea Edulis ◽

Bonamia Ostreae ◽

Differential Gene ◽

Flat Oyster

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Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1

BMC Medical Genomics ◽

10.1186/s12920-018-0443-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 4

Author(s):

Sun Young Lee ◽

Yong Kwang Park ◽

Cheol-Hee Yoon ◽

Kisoon Kim ◽

Kyung-Chang Kim

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Meta Analysis ◽

Gene Expression Profiles ◽

Hiv 1

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PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00128.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. L684-L697 ◽

Cited By ~ 7

Author(s):

Valentina Biasin ◽

Slaven Crnkovic ◽

Anita Sahu-Osen ◽

Anna Birnhuber ◽

Elie El Agha ◽

...

Keyword(s):

Gene Expression ◽

Pulmonary Fibrosis ◽

Expression Profiles ◽

Smooth Muscle Actin ◽

Gene Expression Profiles ◽

Mesenchymal Cell ◽

Cellular Heterogeneity ◽

Cell Populations ◽

Variable Expression ◽

Distinct Gene

Pulmonary fibrosis is characterized by pronounced collagen deposition and myofibroblast expansion, whose origin and plasticity remain elusive. We utilized a fate-mapping approach to investigate α-smooth muscle actin (αSMA)+ and platelet-derived growth factor receptor α (PDGFRα)+ cells in two lung fibrosis models, complemented by cell type-specific next-generation sequencing and investigations on human lungs. Our data revealed that αSMA+ and PDGFRα+ cells mark two distinct mesenchymal lineages with minimal transdifferentiation potential during lung fibrotic remodeling. Parenchymal and perivascular fibrotic regions were populated predominantly with PDGFRα+ cells expressing collagen, while αSMA+ cells in the parenchyma and vessel wall showed variable expression of collagen and the contractile protein desmin. The distinct gene expression profile found in normal conditions was retained during pathologic remodeling. Cumulatively, our findings identify αSMA+ and PDGFRα+ cells as two separate lineages with distinct gene expression profiles in adult lungs. This cellular heterogeneity suggests that anti-fibrotic therapy should target diverse cell populations.

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Identification of Monotonically Differentially Expressed Genes for IFN-β-Treated Multiple Sclerosis Patients

BioMed Research International ◽

10.1155/2019/5647902 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Suyan Tian ◽

Lei Zhang

Keyword(s):

Gene Expression ◽

Multiple Sclerosis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Biologically Relevant ◽

Therapeutic Mechanism ◽

The Central Nervous System ◽

Multiple Sclerosis Patients ◽

Term Response

Multiple sclerosis (MS) is a common neurological disability of the central nervous system. Immune-modulatory therapy with interferon-β (IFN-β) has been used as a first-line treatment to prevent relapses in MS patients. While the therapeutic mechanism of IFN-β has not been fully elucidated, the data of microarray experiments that collected longitudinal gene expression profiles to evaluate the long-term response of IFN-β treatment have been analyzed using statistical methods that were incapable of dealing with such data. In this study, the GeneRank method was applied to generate weighted gene expression values and the monotonically expressed genes (MEGs) for both IFN-β treatment responders and nonresponders were identified. The proposed procedure identified 13 MEGs for the responders and 2 MEGs for the nonresponders, most of which are biologically relevant to MS. Our work here provides some useful insight into the mechanism of IFN-β treatment for MS patients. A full understanding of the therapeutic mechanism will enable a more personalized treatment strategy possible.

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