scholarly journals Regulatory Mechanisms of Mitochondrial Function and Cardiac Aging

2020 ◽  
Vol 21 (4) ◽  
pp. 1359 ◽  
Author(s):  
Ruizhu Lin ◽  
Risto Kerkelä
Keyword(s):  
Cellular Aging ◽  
Regulatory Mechanisms ◽  
Cell Type ◽  
Key Factors ◽  
Regenerative Capacity ◽  
Cardiac Aging ◽  
Differentiated Cells ◽  
Mitochondrial Population ◽  
Recent Advancement ◽  
And Function

Aging is a major risk factor for cardiovascular diseases (CVDs), the major cause of death worldwide. Cardiac myocytes, which hold the most abundant mitochondrial population, are terminally differentiated cells with diminished regenerative capacity in the adult. Cardiomyocyte mitochondrial dysfunction is a characteristic feature of the aging heart and one out of the nine features of cellular aging. Aging and cardiac pathologies are also associated with increased senescence in the heart. However, the cause and consequences of cardiac senescence during aging or in cardiac pathologies are mostly unrecognized. Further, despite recent advancement in anti-senescence therapy, the targeted cell type and the effect on cardiac structure and function have been largely overlooked. The unique cellular composition of the heart, and especially the functional properties of cardiomyocytes, need to be considered when designing therapeutics to target cardiac aging. Here we review recent findings regarding key factors regulating cell senescence, mitochondrial health as well as cardiomyocyte rejuvenation.

scholarly journals Differential Regulation of Gonadotropins as Revealed by Transcriptomes of Distinct LH and FSH Cells of Fish Pituitary

2021 ◽  
Vol 22 (12) ◽  
pp. 6478
Author(s):  
Lian Hollander-Cohen ◽  
Matan Golan ◽  
Berta Levavi-Sivan
Keyword(s):  
Follicle Stimulating Hormone ◽  
Differential Regulation ◽  
Receptor Expression ◽  
Hormone Regulation ◽  
Fish Reproduction ◽  
Cell Type ◽  
Conserved Genes ◽  
Transgenic Tilapia ◽  
And Function ◽  
Direct Regulation

From mammals to fish, reproduction is driven by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) temporally secreted from the pituitary gland. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin cell since, unlike mammals, they synthesize and secrete LH and FSH from distinct cells. Only very distant vertebrate classes (such as fish and birds) demonstrate the mono-hormonal strategy, suggesting a potential convergent evolution. Cell-specific transcriptome analysis of double-labeled transgenic tilapia expressing GFP and RFP in LH or FSH cells, respectively, yielded genes specifically enriched in each cell type, revealing differences in hormone regulation, receptor expression, cell signaling, and electrical properties. Each cell type expresses a unique GPCR signature that reveals the direct regulation of metabolic and homeostatic hormones. Comparing these novel transcriptomes to that of rat gonadotrophs revealed conserved genes that might specifically contribute to each gonadotropin activity in mammals, suggesting conserved mechanisms controlling the differential regulation of gonadotropins in vertebrates.

scholarly journals Cell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christopher A. Brosnan ◽  
Alexander J. Palmer ◽  
Steven Zuryn
Keyword(s):  
Caenorhabditis Elegans ◽  
Regulatory Networks ◽  
Regulatory Mechanisms ◽  
Cell Type ◽  
A Genome ◽  
Temporal Flexibility ◽  
Small Regulatory Rnas ◽  
Cell Type Specific ◽  
Single Cell Type ◽  
Regulated Gene Expression

AbstractMulticellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.

scholarly journals Toxins and Other Bioactive Metabolites in Deep Chlorophyll Layers Containing the Cyanobacteria Planktothrix cf. isothrix in Two Georgian Bay Embayments, Lake Huron

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 445
Author(s):  
Arthur Zastepa ◽  
Todd R. Miller ◽  
L. Cynthia Watson ◽  
Hedy Kling ◽  
Susan B. Watson
Keyword(s):  
Thermal Stratification ◽  
Chemical Defence ◽  
Euphotic Zone ◽  
Lake Huron ◽  
Metabolic Inhibitors ◽  
Bioactive Metabolites ◽  
Total Biomass ◽  
Key Factors ◽  
Georgian Bay ◽  
And Function

The understanding of deep chlorophyll layers (DCLs) in the Great Lakes—largely reported as a mix of picoplankton and mixotrophic nanoflagellates—is predominantly based on studies of deep (>30 m), offshore locations. Here, we document and characterize nearshore DCLs from two meso-oligotrophic embayments, Twelve Mile Bay (TMB) and South Bay (SB), along eastern Georgian Bay, Lake Huron (Ontario, Canada) in 2014, 2015, and 2018. Both embayments showed the annual formation of DCLs, present as dense, thin, metalimnetic plates dominated by the large, potentially toxic, and bloom-forming cyanobacteria Planktothrix cf. isothrix. The contribution of P. cf. isothrix to the deep-living total biomass (TB) increased as thermal stratification progressed over the ice-free season, reaching 40% in TMB (0.6 mg/L at 9.5 m) and 65% in South Bay (3.5 mg/L at 7.5 m) in 2015. The euphotic zone in each embayment extended down past the mixed layer, into the nutrient-enriched hypoxic hypolimnia, consistent with other studies of similar systems with DCLs. The co-occurrence of the metal-oxidizing bacteria Leptothrix spp. and bactivorous flagellates within the metalimnetic DCLs suggests that the microbial loop plays an important role in recycling nutrients within these layers, particularly phosphate (PO4) and iron (Fe). Samples taken through the water column in both embayments showed measurable concentrations of the cyanobacterial toxins microcystins (max. 0.4 µg/L) and the other bioactive metabolites anabaenopeptins (max. ~7 µg/L) and cyanopeptolins (max. 1 ng/L), along with the corresponding genes (max. in 2018). These oligopeptides are known to act as metabolic inhibitors (e.g., in chemical defence against grazers, parasites) and allow a competitive advantage. In TMB, the 2018 peaks in these oligopeptides and genes coincided with the P. cf. isothrix DCLs, suggesting this species as the main source. Our data indicate that intersecting physicochemical gradients of light and nutrient-enriched hypoxic hypolimnia are key factors in supporting DCLs in TMB and SB. Microbial activity and allelopathy may also influence DCL community structure and function, and require further investigation, particularly related to the dominance of potentially toxigenic species such as P. cf. isothrix.

scholarly journals Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3951
Author(s):  
Sarva Keihani ◽  
Verena Kluever ◽  
Eugenio F. Fornasiero
Keyword(s):  
Neuronal Differentiation ◽  
Neuronal Excitability ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Regulatory Mechanisms ◽  
Control Robustness ◽  
Living Organisms ◽  
And Function ◽  
Regulatory Functions ◽  
Neuronal Physiology

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

scholarly journals Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amitava Basu ◽  
Vijay K. Tiwari
Keyword(s):  
Regenerative Medicine ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Specific Cell ◽  
Cell Type ◽  
Pathological Conditions ◽  
Gene Regulatory ◽  
Induced Pluripotent ◽  
And Function

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

scholarly journals TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-chi Shen ◽  
Adrienne Niederriter Shami ◽  
Lindsay Moritz ◽  
Hailey Larose ◽  
Gabriel L. Manske ◽  
...  
Keyword(s):  
Tissue Homeostasis ◽  
Testicular Development ◽  
Myoid Cells ◽  
Regenerative Capacity ◽  
Adult Testis ◽  
Mesenchymal Progenitors ◽  
And Function ◽  
Potential Reserve ◽  
Resident Fibroblast

AbstractTesticular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that TCF21lin cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. In vitro, TCF21lin cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, TCF21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be potentially leveraged in development of future therapies for hypoandrogenism and/or infertility.

scholarly journals Myosins in Osteoclast Formation and Function

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 157 ◽  
Author(s):  
Beth Lee
Keyword(s):  
Actin Cytoskeleton ◽  
Motor Proteins ◽  
Current Knowledge ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Bone Modeling ◽  
Cell Type ◽  
And Function ◽  
Bone Modeling And Remodeling

Skeletal quantity and quality are determined by processes of bone modeling and remodeling, which are undertaken by cells that build and resorb bone as they respond to mechanical, hormonal, and other external and internal signals. As the sole bone resorptive cell type, osteoclasts possess a remarkably dynamic actin cytoskeleton that drives their function in this enterprise. Actin rearrangements guide osteoclasts’ capacity for precursor fusion during differentiation, for migration across bone surfaces and sensing of their composition, and for generation of unique actin superstructures required for the resorptive process. In this regard, it is not surprising that myosins, the superfamily of actin-based motor proteins, play key roles in osteoclast physiology. This review briefly summarizes current knowledge of the osteoclast actin cytoskeleton and describes myosins’ roles in osteoclast differentiation, migration, and actin superstructure patterning.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

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