scholarly journals Regulatory links between imprinted genes: evolutionary predictions and consequences

2016 ◽  
Vol 283 (1824) ◽  
pp. 20152760 ◽  
Author(s):  
Manus M. Patten ◽  
Michael Cowley ◽  
Rebecca J. Oakey ◽  
Robert Feil
Keyword(s):  
Gene Networks ◽  
Cellular Proliferation ◽  
Point Of View ◽  
Imprinted Genes ◽  
Imprinted Gene ◽  
Genome Wide ◽  
Proliferation And Differentiation ◽  
Evolutionary View ◽  
In Trans ◽  
Regulatory Effects

Genomic imprinting is essential for development and growth and plays diverse roles in physiology and behaviour. Imprinted genes have traditionally been studied in isolation or in clusters with respect to cis -acting modes of gene regulation, both from a mechanistic and evolutionary point of view. Recent studies in mammals, however, reveal that imprinted genes are often co-regulated and are part of a gene network involved in the control of cellular proliferation and differentiation. Moreover, a subset of imprinted genes acts in trans on the expression of other imprinted genes. Numerous studies have modulated levels of imprinted gene expression to explore phenotypic and gene regulatory consequences. Increasingly, the applied genome-wide approaches highlight how perturbation of one imprinted gene may affect other maternally or paternally expressed genes. Here, we discuss these novel findings and consider evolutionary theories that offer a rationale for such intricate interactions among imprinted genes. An evolutionary view of these trans -regulatory effects provides a novel interpretation of the logic of gene networks within species and has implications for the origin of reproductive isolation between species.

scholarly journals Double paternal uniparental isodisomy 7 and 15 presenting with Beckwith-Wiedemann spectrum features

2021 ◽  
pp. mcs.a006113
Author(s):  
Siren Berland ◽  
Cecilie Fremstad Rustad ◽  
Mariann Haavik Lysfjord Bentsen ◽  
Embjorg Julianne Wollen ◽  
Gitta Turowski ◽  
...  
Keyword(s):  
Imprinted Genes ◽  
Promoting Effect ◽  
Monosomy 7 ◽  
Imprinted Gene ◽  
Patient Fibroblast ◽  
Gene Sets ◽  
Genome Wide ◽  
Uniparental Isodisomy ◽  
Show Evidence ◽  
Conjugated Hyperbilirubinemia

Here we describe for the first time double paternal uniparental isodisomy (iUPD) 7 and 15 in a baby boy with features in the Beckwith-Wiedemann syndrome spectrum (BWSp) (placentomegaly, hyperinsulinism, enlarged viscera, hemangiomas, and earlobe creases) in addition to conjugated hyperbilirubinemia. His phenotype was also reminiscent of genome-wide paternal uniparental isodisomy. We discuss the most likely origin of the UPDs; a maternal double monosomy 7 and 15 rescued by duplication of the paternal chromosomes after fertilization. So far, paternal UPD7 is not associated with an abnormal phenotype, while paternal UPD15 causes Angelman syndrome. Methylation analysis for other clinically relevant imprinting disorders, including BWSp, was normal. Therefore, we hypothesized that the double UPD affected other imprinted genes. To look for such effects, patient fibroblast RNA was isolated and analyzed for differential expression compared to six controls. We did not find apparent transcription differences in imprinted genes outside chromosomes 7 and 15 in patient fibroblast. PEG10 (7q21.3) was the only paternally imprinted gene on these chromosomes upregulated beyond double-dose expectation (6-fold). We speculate that a high PEG10 level could have a growth-promoting effect as his phenotype was not related to aberrations in BWS-locus on 11p15.5 after DNA, RNA, and methylation testing. However, many genes in gene sets associated with growth were upregulated. This case broadens the phenotypic spectrum of UPDs but did not show evidence of involvement of an imprinted gene network.

scholarly journals A genome-wide search for new imprinted genes in the human placenta identifies DSCAM as the first imprinted gene on chromosome 21

2018 ◽  
Vol 27 (1) ◽  
pp. 49-60 ◽  
Author(s):  
Laïla Allach El Khattabi ◽  
Stéphanie Backer ◽  
Amélie Pinard ◽  
Marie-Noëlle Dieudonné ◽  
Vassilis Tsatsaris ◽  
...  
Keyword(s):  
Human Placenta ◽  
Chromosome 21 ◽  
Imprinted Genes ◽  
Imprinted Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Search

scholarly journals Dynamic Expression of Imprinted Genes in the Developing and Postnatal Pituitary Gland

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 509
Author(s):  
Valeria Scagliotti ◽  
Ruben Costa Fernandes Esse ◽  
Thea L. Willis ◽  
Mark Howard ◽  
Isabella Carrus ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Rna Sequencing ◽  
Gene Networks ◽  
Current Knowledge ◽  
High Sensitivity ◽  
Imprinted Genes ◽  
Sequencing Data ◽  
Dynamic Regulation ◽  
Imprinted Gene ◽  
And Function

In mammals, imprinted genes regulate many critical endocrine processes such as growth, the onset of puberty and maternal reproductive behaviour. Human imprinting disorders (IDs) are caused by genetic and epigenetic mechanisms that alter the expression dosage of imprinted genes. Due to improvements in diagnosis, increasing numbers of patients with IDs are now identified and monitored across their lifetimes. Seminal work has revealed that IDs have a strong endocrine component, yet the contribution of imprinted gene products in the development and function of the hypothalamo-pituitary axis are not well defined. Postnatal endocrine processes are dependent upon the production of hormones from the pituitary gland. While the actions of a few imprinted genes in pituitary development and function have been described, to date there has been no attempt to link the expression of these genes as a class to the formation and function of this essential organ. This is important because IDs show considerable overlap, and imprinted genes are known to define a transcriptional network related to organ growth. This knowledge deficit is partly due to technical difficulties in obtaining useful transcriptomic data from the pituitary gland, namely, its small size during development and cellular complexity in maturity. Here we utilise high-sensitivity RNA sequencing at the embryonic stages, and single-cell RNA sequencing data to describe the imprinted transcriptome of the pituitary gland. In concert, we provide a comprehensive literature review of the current knowledge of the role of imprinted genes in pituitary hormonal pathways and how these relate to IDs. We present new data that implicate imprinted gene networks in the development of the gland and in the stem cell compartment. Furthermore, we suggest novel roles for individual imprinted genes in the aetiology of IDs. Finally, we describe the dynamic regulation of imprinted genes in the pituitary gland of the pregnant mother, with implications for the regulation of maternal metabolic adaptations to pregnancy.

scholarly journals Systematic investigation of imprinted gene expression and enrichment in the mouse brain explored at single-cell resolution

2020 ◽  
Author(s):  
M. J. Higgs ◽  
M. J. Hill ◽  
R. M. John ◽  
A. R. Isles
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Gene Networks ◽  
Cell Types ◽  
Brain Regions ◽  
Systematic Investigation ◽  
Adult Brain ◽  
Imprinted Genes ◽  
Imprinted Gene ◽  
The Brain

AbstractAlthough a number of imprinted genes are known to be highly expressed in the brain, and in certain brain regions in particular, whether they are truly over-represented in the brain has never been formally tested. Using fifteen single-cell RNA sequencing datasets we take a systematic approach to investigate imprinted gene over-representation at the organ, brain region, and cell-specific levels. We establish that imprinted genes are indeed over-represented in the adult brain, and in neurons particularly compared to other brain cell-types. We then examine brain-wide datasets to examine enrichment within distinct regions of the brain and demonstrate over-representation of imprinted genes in the hypothalamus, ventral midbrain, pons and medulla. Finally, using datasets focusing on these regions of enrichment, we were able to identify hypothalamic neuroendocrine populations and the monoaminergic hindbrain neurons as specific hotspots of imprinted gene expression. These analyses provide the first robust assessment of the neural systems on which imprinted genes converge. Moreover, the unbiased approach, with each analysis informed by the findings of the previous level, permits highly informed inferences about the functions on which imprinted genes converge. Our findings indicate the neuronal regulation of motivated behaviours such as feeding, parental behaviour and sleep as functional hotspots for imprinting, thus adding statistically rigour to prior assumptions and providing testable predictions for novel neural and behavioural phenotypes associated with specific genes and imprinted gene networks. In turn, this work sheds further light on the potential evolutionary drivers of genomic imprinting in the brain.

Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

2021 ◽  
Vol 16 (1) ◽  
pp. 3-13
Author(s):  
Lang Wang ◽  
Yong Li ◽  
Maorui Zhang ◽  
Kui Huang ◽  
Shuanglin Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Adult Stem Cells ◽  
Adipose Derived Stem Cells ◽  
Proliferation And Differentiation ◽  
Recent Developments ◽  
Good Biocompatibility ◽  
Regulatory Effects ◽  
New Treatment

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.

scholarly journals The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanxiu Sun ◽  
Yu Yuan ◽  
Wei Wu ◽  
Le Lei ◽  
Lingli Zhang
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Differentiation Potential ◽  
Stem Cell Fate ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Adipocytic Differentiation ◽  
Regulatory Effects ◽  
Insight Into ◽  
Mechanical Regulation

AbstractBone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.

scholarly journals Detecting Genetic Associations betweenATG5and Lupus Nephritis bytrans-eQTL

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yue-miao Zhang ◽  
Fa-juan Cheng ◽  
Xu-jie Zhou ◽  
Yuan-yuan Qi ◽  
Ping Hou ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Information ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Genome Wide ◽  
Custom Made ◽  
Regulatory Effects

Objectives. Numerous loci were identified to perturb gene expression intrans. As elevatedATG5expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated withATG5expression in a Chinese population with lupus nephritis (LN).Methods. The online expression quantitative trait loci database was searched fortrans-expression single nucleotide polymorphisms (trans-eSNPs) ofATG5. Taggingtrans-eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed.Results. Fourtrans-eSNPs were observed to be associated with susceptibility to LN (P< 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven othertrans-eSNPs showed marginal significant associations (0.05 <P< 0.1). Correlations between thetrans-eSNPs andATG5expression and different expression levels ofATG5in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes oftrans-eSNPs and severity or outcome of the patients.Conclusion. Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.

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