scholarly journals A mouse tissue atlas of small non-coding RNA

2018 ◽  
Author(s):  
Alina Isakova ◽  
Tobias Fehlmann ◽  
Andreas Keller ◽  
Stephen R. Quake

SUMMARYSmall non-coding RNAs (ncRNAs) play a vital role in a broad range of biological processes both in health and disease. A comprehensive quantitative reference of small ncRNA expression would significantly advance our understanding of ncRNA roles in shaping tissue functions. Here, we systematically profiled the levels of five ncRNA classes (miRNA, snoRNA, snRNA, scaRNA and tRNA fragments) across eleven mouse tissues by deep sequencing. Using fourteen biological replicates spanning both sexes, we identified that ~ 30% of small ncRNAs are distributed across the body in a tissue-specific manner with some are also being sexually dimorphic. We found that miRNAs are subject to “arm switching” between healthy tissues and that tRNA fragments are retained within tissues in both a gene- and a tissue-specific manner. Out of eleven profiled tissues we confirmed that brain contains the largest number of unique small ncRNA transcripts, some of which were previously annotated while others are identified for the first time in this study. Furthermore, by combining these findings with single-cell ATAC-seq data, we were able to connect identified brain-specific ncRNA with their cell types of origin. These results yield the most comprehensive characterization of specific and ubiquitous small RNAs in individual murine tissues to date, and we expect that this data will be a resource for the further identification of ncRNAs involved in tissue-function in health and dysfunction in disease.HIGHLIGHTS-An atlas of tissue levels of multiple small ncRNA classes generated from 14 biological replicates of both sexes across 11 tissues-Distinct distribution patterns of miRNA arms and tRNA fragments across tissues suggest the existence of tissue-specific mechanisms of ncRNA cleavage and retention-miRNA expression is sex specific in healthy tissues-Small RNA-seq and scATAC-seq data integration produce a detailed map of cell-type specific ncRNA profiles in the mouse brain

2020 ◽  
Vol 117 (41) ◽  
pp. 25634-25645
Author(s):  
Alina Isakova ◽  
Tobias Fehlmann ◽  
Andreas Keller ◽  
Stephen R. Quake

Small noncoding RNAs (ncRNAs) play a vital role in a broad range of biological processes both in health and disease. A comprehensive quantitative reference of small ncRNA expression would significantly advance our understanding of ncRNA roles in shaping tissue functions. Here, we systematically profiled the levels of five ncRNA classes (microRNA [miRNA], small nucleolar RNA [snoRNA], small nuclear RNA [snRNA], small Cajal body-specific RNA [scaRNA], and transfer RNA [tRNA] fragments) across 11 mouse tissues by deep sequencing. Using 14 biological replicates spanning both sexes, we identified that ∼30% of small ncRNAs are distributed across the body in a tissue-specific manner with some also being sexually dimorphic. We found that some miRNAs are subject to “arm switching” between healthy tissues and that tRNA fragments are retained within tissues in both a gene- and a tissue-specific manner. Out of 11 profiled tissues, we confirmed that brain contains the largest number of unique small ncRNA transcripts, some of which were previously annotated while others are identified in this study. Furthermore, by combining these findings with single-cell chromatin accessibility (scATAC-seq) data, we were able to connect identified brain-specific ncRNAs with their cell types of origin. These results yield the most comprehensive characterization of specific and ubiquitous small RNAs in individual murine tissues to date, and we expect that these data will be a resource for the further identification of ncRNAs involved in tissue function in health and dysfunction in disease.


Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 452
Author(s):  
Lauren M. Ashwood ◽  
Michela L. Mitchell ◽  
Bruno Madio ◽  
David A. Hurwood ◽  
Glenn F. King ◽  
...  

Phylum Cnidaria is an ancient venomous group defined by the presence of cnidae, specialised organelles that serve as venom delivery systems. The distribution of cnidae across the body plan is linked to regionalisation of venom production, with tissue-specific venom composition observed in multiple actiniarian species. In this study, we assess whether morphological variants of tentacles are associated with distinct toxin expression profiles and investigate the functional significance of specialised tentacular structures. Using five sea anemone species, we analysed differential expression of toxin-like transcripts and found that expression levels differ significantly across tentacular structures when substantial morphological variation is present. Therefore, the differential expression of toxin genes is associated with morphological variation of tentacular structures in a tissue-specific manner. Furthermore, the unique toxin profile of spherical tentacular structures in families Aliciidae and Thalassianthidae indicate that vesicles and nematospheres may function to protect branched structures that host a large number of photosynthetic symbionts. Thus, hosting zooxanthellae may account for the tentacle-specific toxin expression profiles observed in the current study. Overall, specialised tentacular structures serve unique ecological roles and, in order to fulfil their functions, they possess distinct venom cocktails.


2021 ◽  
Author(s):  
Sadia Sheraz ◽  
Yongfang Wan ◽  
Eudri Venter ◽  
Shailender K Verma ◽  
Qing Xiong ◽  
...  

AbstractUnderstanding iron trafficking in plants is key to enhancing the nutritional quality of crops. Due to the difficulty of imaging iron in transit, little is known about iron translocation and distribution in developing seeds. A novel approach, combining 57Fe isotope labelling and NanoSIMS, was used to visualize iron translocation dynamics at the subcellular level in wheat grain, Triticum aestivum L. We were able to track the main route of iron from maternal tissues to the embryo through different cell types. Further evidence for this route was provided by genetically diverting iron into storage vacuoles, as confirmed by histological staining and TEM-EDS. Virtually all iron was found in intracellular bodies, indicating symplastic rather than apoplastic transport. Aleurone cells contained a new type of iron body, highly enriched in 57Fe, and most likely represents iron-nicotianamine being delivered to phytate globoids. Correlation with tissue-specific gene expression provides an updated model of iron homeostasis in cereal grains with relevance for future biofortification efforts.


2019 ◽  
Author(s):  
Robin L. Armstrong ◽  
Souradip Das ◽  
Christina A. Hill ◽  
Robert J. Duronio ◽  
Jared T. Nordman

AbstractReplication initiation in eukaryotic cells occurs asynchronously throughout S phase, yielding early and late replicating regions of the genome, a process known as replication timing (RT). RT changes during development to ensure accurate genome duplication and maintain genome stability. To understand the relative contributions that cell lineage, cell cycle, and replication initiation regulators have on RT, we utilized the powerful developmental systems available in Drosophila melanogaster. We generated and compared RT profiles from mitotic cells of different tissues and from mitotic and endocycling cells of the same tissue. Our results demonstrate that cell lineage has the largest effect on RT, whereas switching from a mitotic to an endoreplicative cell cycle has little to no effect on RT. Additionally, we demonstrate that the RT differences we observed in all cases are largely independent of transcriptional differences. We also employed a genetic approach in these same cell types to understand the relative contribution the eukaryotic RT control factor, Rif1, has on RT control. Our results demonstrate that Rif1 can function in a tissue-specific manner to control RT. Importantly, the Protein Phosphatase 1 (PP1) binding motif of Rif1 is essential for Rif1 to regulate RT. Together, our data support a model in which the RT program is primarily driven by cell lineage and is further refined by Rif1/PP1 to ultimately generate tissue-specific RT programs.


2016 ◽  
Vol 113 (13) ◽  
pp. E1826-E1834 ◽  
Author(s):  
Roni Lehmann-Werman ◽  
Daniel Neiman ◽  
Hai Zemmour ◽  
Joshua Moss ◽  
Judith Magenheim ◽  
...  

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.


1996 ◽  
Vol 318 (1) ◽  
pp. 297-303 ◽  
Author(s):  
Guy W MAINWARING ◽  
Sally M WILLIAMS ◽  
John R FOSTER ◽  
Jonathan TUGWOOD ◽  
Trevor GREEN

Two murine Theta-class glutathione S-transferases (GSTs), mGSTT1 and mGSTT2, have been cloned and sequenced. The murine cDNAs, together with the published sequences of the rat and human enzymes, were used to design oligonucleotide probes in order to determine the distribution of mRNA for these enzymes in the liver and lung of rat, mouse and human. The mRNA distribution was compared with that of enzyme protein determined with an antibody to rat GSTT2–2. Both the antibody and the oligonucleotide probes gave the same distribution patterns. Both enzymes were present at significantly higher concentrations in mouse tissues than in rat or human tissues. In mouse liver, both enzymes were localized in specific cell types and in nuclei. Although the distribution of GSTT2–2 in rat liver was similar to that seen in the mouse, GSTT1–1 was not localized in a specific cell type or in the nuclei of either rat or human liver. In the lungs, very high concentrations of the Theta enzymes were present in mouse-lung Clara cells and ciliated cells, with much lower levels in the Clara cells only of rat lung. Low levels of human transferase GSTT1–1 were detected in a small number of Clara cells and ciliated cells at the alveolar/bronchiolar junction. The relative activities between species, and the cellular and sub-cellular distribution within the liver and lungs of each species, provides an explanation for the species-specificity of methylene chloride, a mouse-specific carcinogen activated by glutathione S-transferase GSTT1–1.


Genetics ◽  
2020 ◽  
Vol 215 (1) ◽  
pp. 75-87 ◽  
Author(s):  
Robin L. Armstrong ◽  
Souradip Das ◽  
Christina A. Hill ◽  
Robert J. Duronio ◽  
Jared T. Nordman

Replication initiation in eukaryotic cells occurs asynchronously throughout S phase, yielding early- and late-replicating regions of the genome, a process known as replication timing (RT). RT changes during development to ensure accurate genome duplication and maintain genome stability. To understand the relative contributions that cell lineage, cell cycle, and replication initiation regulators have on RT, we utilized the powerful developmental systems available in Drosophila melanogaster. We generated and compared RT profiles from mitotic cells of different tissues and from mitotic and endocycling cells of the same tissue. Our results demonstrate that cell lineage has the largest effect on RT, whereas switching from a mitotic to an endoreplicative cell cycle has little to no effect on RT. Additionally, we demonstrate that the RT differences we observed in all cases are largely independent of transcriptional differences. We also employed a genetic approach in these same cell types to understand the relative contribution the eukaryotic RT control factor, Rif1, has on RT control. Our results demonstrate that Rif1 can function in a tissue-specific manner to control RT. Importantly, the Protein Phosphatase 1 (PP1) binding motif of Rif1 is essential for Rif1 to regulate RT. Together, our data support a model in which the RT program is primarily driven by cell lineage and is further refined by Rif1/PP1 to ultimately generate tissue-specific RT programs.


2007 ◽  
Vol 55 (10) ◽  
pp. 1039-1048 ◽  
Author(s):  
Robert Schmalzigaug ◽  
Hyewon Phee ◽  
Collin E. Davidson ◽  
Arthur Weiss ◽  
Richard T. Premont

GIT1 and GIT2 belong to the family of ADP-ribosylation factor GTPase-activating proteins (ARF-GAP) and have been implicated in the regulation of G protein-coupled receptor sequestration, cell migration, T-cell activation, neuronal spine formation, and aggregate formation in Huntington's disease. Examination of endogenous GIT protein expression in tissues, however, has been hampered by the lack of GIT2-specific antibodies. To visualize GIT1 and GIT2 gene expression in mouse tissues, we created mice with β-galactosidase (β-Gal) reporters inserted into the two GIT genes. β-Gal staining confirmed the broad tissue distribution of GIT1 and GIT2 in the mouse but also revealed striking differences. GIT2 is expressed in most cells of the body, whereas GIT1 is restricted to only a subset of cells. For example, GIT2 is uniformly expressed throughout lung and liver, whereas GIT1 is restricted to cells lining blood vessels, bronchi, and bile ducts. Expression of GIT1 and GIT2 is mutually exclusive in the testes, where a developmental expression shift occurs, with GIT2 present in spermatogonia but GIT1 in mature spermatids. In conclusion, analysis of endogenous GIT expression revealed a nearly ubiquitous distribution of GIT2, whereas GIT1 is restricted to specific cell types even in tissues with apparently high GIT1 expression and is entirely absent from some tissues. (J Histochem Cytochem 55: 1039–1048, 2007)


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Ziyi Chen ◽  
Anfei Huang ◽  
Jiya Sun ◽  
Taijiao Jiang ◽  
F. Xiao-Feng Qin ◽  
...  

Abstract Mice are some of the widely used experimental animal models for studying human diseases. Defining the compositions of immune cell populations in various tissues from experimental mouse models is critical to understanding the involvement of immune responses in various physiological and patho-physiological conditions. However, non-lymphoid tissues are normally composed of vast and diverse cellular components, which make it difficult to quantify the relative proportions of immune cell types. Here we report the development of a computational algorithm, ImmuCC, to infer the relative compositions of 25 immune cell types in mouse tissues using microarray-based mRNA expression data. The ImmuCC algorithm showed good performance and robustness in many simulated datasets. Remarkable concordances were observed when ImmuCC was used on three public datasets, one including enriched immune cells, one with normal single positive T cells, and one with leukemia cell samples. To validate the performance of ImmuCC objectively, thorough cross-comparison of ImmuCC predicted compositions and flow cytometry results was done with in-house generated datasets collected from four distinct mouse lymphoid tissues and three different types of tumor tissues. The good correlation and biologically meaningful results demonstrate the broad utility of ImmuCC for assessing immune cell composition in diverse mouse tissues under various conditions.


2019 ◽  
Author(s):  
Jun’e Liu ◽  
Kai Li ◽  
Jiabin Cai ◽  
Mingchang Zhang ◽  
Xiaoting Zhang ◽  
...  

SUMMARYN6-methyladenosine (m6A), the most abundant internal mRNA modification, and N6,2’-O-dimethyladenosine (m6Am), found at the first-transcribed nucleotide, are two examples of dynamic and reversible epitranscriptomic marks. However, the profiles and distribution patterns of m6A and m6Am across different human and mouse tissues are poorly characterized. Here we report the m6A and m6Am methylome through an extensive profiling of 42 human tissues and 16 mouse tissue samples. Globally, the m6A and m6Am peaks in non-brain tissues demonstrates mild tissue-specificity but are correlated in general, whereas the m6A and m6Am methylomes of brain tissues are clearly resolved from the non-brain tissues. Nevertheless, we identified a small subset of tissue-specific m6A peaks that can readily classify the tissue types. The number of m6A and m6Am peaks are partially correlated with the expression levels of their writers and erasers. In addition, the m6A- and m6Am-containing regions are enriched for single nucleotide polymorphisms. Furthermore, cross-species analysis of m6A and m6Am methylomes revealed that species, rather than tissue types, is the primary determinant of methylation. Collectively, our study provides an in-depth resource for dissecting the landscape and regulation of the m6A and m6Am epitranscriptomic marks across mammalian tissues.


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