Change search
Refine search result
1 - 13 of 13
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Brandão, Luiz Eduardo Mateus
    et al.
    Espes, Daniel
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Martikainen, Teemu
    Westerlund, Nestori
    Lampola, Lauri
    Popa, Alexandru
    Vogel, Heike
    Schürmann, Annette
    Dickson, Suzanne L.
    Benedict, Christian
    Cedernaes, Jonathan
    Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial2022In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 31, no 2, article id e13472Article in journal (Refereed)
    Abstract [en]

    The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep–wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (~27%–30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.

  • 2. Bruhn-Olszewska, Bożena
    et al.
    Davies, Hanna
    Sarkisyan, Daniil
    Juhas, Ulana
    Rychlicka-Buniowska, Edyta
    Wójcik, Magdalena
    Horbacz, Monika
    Jąkalski, Marcin
    Olszewski, Paweł
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Smialowska, Agata
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Wierzba, Karol
    Naluai, Åsa Torinsson
    Jern, Niklas
    Andersson, Lars-Magnus
    Järhult, Josef D.
    Filipowicz, Natalia
    Janson, Eva Tiensuu
    Rubertsson, Sten
    Lipcsey, Miklós
    Gisslén, Magnus
    Hultström, Michael
    Frithiof, Robert
    Dumanski, Jan P.
    Loss of Y in leukocytes as a risk factor for critical COVID-19 in men2022In: Genome Medicine, E-ISSN 1756-994X, Vol. 14, no 1, article id 139Article in journal (Refereed)
    Abstract [en]

    Background: The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.

    Methods: Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.

    Results: Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93–143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e−11).

    Conclusions: We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.

  • 3. Cedernaes, Jonathan
    et al.
    Schonke, Milena
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Mi, Jia
    Chibalin, Alexander
    Voisin, Sarah
    Osler, Megan
    Vogel, Heike
    Hornaeus, Katarina
    Dickson, Suzanne L.
    Lind, Sara Bergstrom
    Bergquist, Jonas
    Schioth, Helgi B.
    Zierath, Juleen R.
    Benedict, Christian
    Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans2018In: Science Advances, E-ISSN 2375-2548, Vol. 4, no 8, article id eaar8590Article in journal (Refereed)
    Abstract [en]

    Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.

  • 4. Coenen-Stass, Anna M. L.
    et al.
    Sork, Helena
    Gatto, Sole
    Godfrey, Caroline
    Bhomra, Amarjit
    Krjutskov, Kaarel
    Hart, Jonathan R.
    Westholm, Jakub O.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    O'Donovan, Liz
    Roos, Andreas
    Lochmueller, Hanns
    Puri, Pier Lorenzo
    EL Andaloussi, Samir
    Wood, Matthew J. A.
    Roberts, Thomas C.
    Comprehensive RNA-Sequencing Analysis in Serum and Muscle Reveals Novel Small RNA Signatures with Biomarker Potential for DMD2018In: Molecular Therapy Nucleic Acids, E-ISSN 2162-2531, Vol. 13, p. 1-15Article in journal (Refereed)
    Abstract [en]

    Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their biological relevance is largely unknown. To investigate the relationship between intracellular and extracellular sRNA levels on a global scale, we performed sRNA sequencing in four muscle types and serum from wild-type, dystrophic mdx, and mdx mice in which dystrophin protein expression was restored by exon skipping. Differentially abundant sRNAs were identified in serum (mapping to miRNA, small nuclear RNA [snRNA], and PIWI-interacting RNA [piRNA] loci). One novel candidate biomarker, miR-483, was increased in both mdx serum and muscle, and also elevated in DMD patient sera. Dystrophin restoration induced global shifts in miRNA (including miR-483) and snRNA-fragment abundance toward wild-type levels. Specific serum piRNA-like sRNAs also responded to exon skipping therapy. Absolute miRNA expression in muscle was positively correlated with abundance in the circulation, although multiple highly expressed miRNAs in muscle were not elevated in mdx serum, suggesting that both passive and selective release mechanisms contribute to serum miRNA levels. In conclusion, this study has revealed new insights into the sRNA biology of dystrophin deficiency and identified novel DMD biomarkers.

  • 5. Ratz, Michael
    et al.
    von Berlin, Leonie
    Larsson, Ludvig
    Martin, Marcel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    La Manno, Gioele
    Lundeberg, Joakim
    Frisén, Jonas
    Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics2022In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 25, no 3, p. 285-294Article in journal (Refereed)
    Abstract [en]

    Ratz et al. present an easy-to-use method to barcode progenitor cells, enabling profiling of cell phenotypes and clonal relations using single-cell and spatial transcriptomics, providing an integrated approach for understanding brain architecture. The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds of molecularly diverse cell types in the nervous system, but the lineage relationships between mature cell types and progenitor cells are not well understood. Here we show in vivo barcoding of early progenitors to simultaneously profile cell phenotypes and clonal relations in the mouse brain using single-cell and spatial transcriptomics. By reconstructing thousands of clones, we discovered fate-restricted progenitor cells in the mouse hippocampal neuroepithelium and show that microglia are derived from few primitive myeloid precursors that massively expand to generate widely dispersed progeny. We combined spatial transcriptomics with clonal barcoding and disentangled migration patterns of clonally related cells in densely labeled tissue sections. Our approach enables high-throughput dense reconstruction of cell phenotypes and clonal relations at the single-cell and tissue level in individual animals and provides an integrated approach for understanding tissue architecture.

  • 6. Sork, Helena
    et al.
    Conceicao, Mariana
    Corso, Giulia
    Nordin, Joel
    Lee, Yi Xin Fiona
    Krjutskov, Kaarel
    Orzechowski Westholm, Jakub
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Vader, Pieter
    Pauwels, Marie
    Vandenbroucke, Roosmarijn E.
    Wood, Matthew J. A.
    EL Andaloussi, Samir
    Mager, Imre
    Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion2021In: Cells, E-ISSN 2073-4409, Vol. 10, no 6, article id 1543Article in journal (Refereed)
    Abstract [en]

    The extracellular environment consists of a plethora of molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, interest in therapeutic short RNA carriers lies mainly in EVs, the vehicles conveying the great majority of the biological activity. Here, by overexpressing miRNA and shRNA sequences in parent cells and using size exclusion liquid chromatography (SEC) to separate the secretome into EV and non-EV fractions, we saw that >98% of overexpressed miRNA was secreted within the non-EV fraction. Furthermore, small RNA sequencing studies of native miRNA transcripts revealed that although the abundance of miRNAs in EVs, non-EVs and parent cells correlated well (R-2 = 0.69-0.87), quantitatively an outstanding 96.2-99.9% of total miRNA was secreted in the non-EV fraction. Nevertheless, though EVs contained only a fraction of secreted miRNAs, these molecules were stable at 37 degrees C in a serum-containing environment, indicating that if sufficient miRNA loading is achieved, EVs can remain delivery-competent for a prolonged period of time. This study suggests that the passive endogenous EV loading strategy might be a relatively wasteful way of loading miRNA to EVs, and active miRNA loading approaches are needed for developing advanced EV miRNA therapies in the future.

  • 7. Sork, Helena
    et al.
    Corso, Giulia
    Krjutskov, Kaarel
    Johansson, Henrik J.
    Nordin, Joel Z.
    Wiklander, Oscar P. B.
    Lee, Yi Xin Fiona
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lehtiö, Janne
    Wood, Matthew J. A.
    Mäger, Imre
    El Andaloussi, Samir
    Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 10813Article in journal (Refereed)
    Abstract [en]

    Extracellular vesicles (EVs) mediate cell-to-cell communication by delivering or displaying macromolecules to their recipient cells. While certain broad-spectrum EV effects reflect their protein cargo composition, others have been attributed to individual EV-loaded molecules such as specific miRNAs. In this work, we have investigated the contents of vesicular cargo using small RNA sequencing of cells and EVs from HEK293T, RD4, C2C12, Neuro2a and C17.2. The majority of RNA content in EVs (49-96%) corresponded to rRNA-, coding-and tRNA fragments, corroborating with our proteomic analysis of HEK293T and C2C12 EVs which showed an enrichment of ribosome and translation-related proteins. On the other hand, the overall proportion of vesicular small RNA was relatively low and variable (2-39%) and mostly comprised of miRNAs and sequences mapping to piRNA loci. Importantly, this is one of the few studies, which systematically links vesicular RNA and protein cargo of vesicles. Our data is particularly useful for future work in unravelling the biological mechanisms underlying vesicular RNA and protein sorting and serves as an important guide in developing EVs as carriers for RNA therapeutics.

  • 8. Ståhl, Patrik L.
    et al.
    Salmen, Fredrik
    Vickovic, Sanja
    Lundmark, Anna
    Navarro, Jose Fernandez
    Magnusson, Jens
    Giacomello, Stefania
    Asp, Michaela
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Huss, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Mollbrink, Annelie
    Linnarsson, Sten
    Codeluppi, Simone
    Borg, Åke
    Ponten, Fredrik
    Costea, Paul Igor
    Sahlen, Pelin
    Mulder, Jan
    Bergmann, Olaf
    Lundeberg, Joakim
    Frisen, Jonas
    Visualization and analysis of gene expression in tissue sections by spatial transcriptomics2016In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 353, no 6294, p. 78-82Article in journal (Refereed)
    Abstract [en]

    Analysis of the pattern of proteins or messenger RNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call spatial transcriptomics, that allows visualization and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections. By positioning histological sections on arrayed reverse transcription primers with unique positional barcodes, we demonstrate high-quality RNA-sequencing data with maintained two-dimensional positional information from the mouse brain and human breast cancer. Spatial transcriptomics provides quantitative gene expression data and visualization of the distribution of mRNAs within tissue sections and enables novel types of bioinformatics analyses, valuable in research and diagnostics.

  • 9. Vickovic, Sanja
    et al.
    Ståhl, Patrik L.
    Salmén, Fredrik
    Giatrellis, Sarantis
    Westholm, Jakub Orzechowski
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Mollbrink, Annelie
    Navarro, Jóse Fernández
    Custodio, Joaquin
    Bienko, Magda
    Sutton, Lesley-Ann
    Rosenquist, Richard
    Frisén, Jonas
    Lundeberg, Joakim
    Massive and parallel expression profiling using microarrayed single-cell sequencing2016In: Nature Communications, E-ISSN 2041-1723, Vol. 7, article id 13182Article in journal (Refereed)
    Abstract [en]

    Single-cell transcriptome analysis overcomes problems inherently associated with averaging gene expression measurements in bulk analysis. However, single-cell analysis is currently challenging in terms of cost, throughput and robustness. Here, we present a method enabling massive microarray-based barcoding of expression patterns in single cells, termed MASC-seq. This technology enables both imaging and high-throughput single-cell analysis, characterizing thousands of single-cell transcriptomes per day at a low cost (0.13 USD/cell), which is two orders of magnitude less than commercially available systems. Our novel approach provides data in a rapid and simple way. Therefore, MASC-seq has the potential to accelerate the study of subtle clonal dynamics and help provide critical insights into disease development and other biological processes.

  • 10. von Berlin, Leonie
    et al.
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Ratz, Michael
    Frisén, Jonas
    Early fate bias in neuroepithelial progenitors of hippocampal neurogenesis2023In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 33, no 4, p. 391-401Article in journal (Refereed)
    Abstract [en]

    Hippocampal adult neural stem cells emerge from progeny of the neuroepithelial lineage during murine brain development. Hippocampus development is increasingly well understood. However, the clonal relationships between early neuroepithelial stem cells and postnatal neurogenic cells remain unclear, especially at the single-cell level. Here we report fate bias and gene expression programs in thousands of clonally related cells in the juvenile hippocampus based on single-cell RNA-seq of barcoded clones. We find evidence for early fate restriction of neuroepithelial stem cells to either neurogenic progenitor cells of the dentate gyrus region or oligodendrogenic, non-neurogenic fate supplying cells for other hippocampal regions including gray matter areas and the Cornu ammonis region 1/3. Our study provides new insights into the phenomenon of early fate restriction guiding the development of postnatal hippocampal neurogenesis.

  • 11. Vromman, Marieke
    et al.
    Anckaert, Jasper
    Bortoluzzi, Stefania
    Buratin, Alessia
    Chen, Chia-Ying
    Chu, Qinjie
    Chuang, Trees-Juen
    Dehghannasiri, Roozbeh
    Dieterich, Christoph
    Dong, Xin
    Flicek, Paul
    Gaffo, Enrico
    Gu, Wanjun
    He, Chunjiang
    Hoffmann, Steve
    Izuogu, Osagie
    Jackson, Michael S.
    Jakobi, Tobias
    Lai, Eric C.
    Nuytens, Justine
    Salzman, Julia
    Santibanez-Koref, Mauro
    Stadler, Peter
    Thas, Olivier
    Eynde, Eveline Vanden
    Verniers, Kimberly
    Wen, Guoxia
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Yang, Li
    Ye, Chu-Yu
    Yigit, Nurten
    Yuan, Guo-Hua
    Zhang, Jinyang
    Zhao, Fangqing
    Vandesompele, Jo
    Volders, Pieter-Jan
    Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision2023In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 20, no 8, p. 1159-1169Article in journal (Refereed)
    Abstract [en]

    The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed using computational tools. Numerous such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools detected more than 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were validated using three orthogonal methods. Generally, tool-specific precision is high and similar (median of 98.8%, 96.3% and 95.5% for qPCR, RNase R and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant differentiators. Of note, precision values are lower when evaluating low-abundance circRNAs. We also show that the tools can be used complementarily to increase detection sensitivity. Finally, we offer recommendations for future circRNA detection and validation. This study describes benchmarking and validation of computational tools for detecting circRNAs, finding most to be highly precise with variations in sensitivity and total detection. The study also finds over 315,000 putative human circRNAs.

  • 12. Zaghlool, Ammar
    et al.
    Ameur, Adam
    Wu, Chenglin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Niazi, Adnan
    Manivannan, Manimozhi
    Bramlett, Kelli
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Uppsala University, Sweden.
    Feuk, Lars
    Expression profiling and in situ screening of circular RNAs in human tissues2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 16953Article in journal (Refereed)
    Abstract [en]

    Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for screening of circRNAs and their linear counterparts in large number of samples. We also applied padlock probes and in situ sequencing to visualize and determine circRNA localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results highlight the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.

  • 13. Zaghlool, Ammar
    et al.
    Niazi, Adnan
    Björklund, Åsa K.
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Ameur, Adam
    Feuk, Lars
    Characterization of the nuclear and cytosolic transcriptomes in human brain tissue reveals new insights into the subcellular distribution of RNA transcripts2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 4076Article in journal (Refereed)
    Abstract [en]

    Transcriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, and interpretation of gene expression signatures in cells. Here, we separated cytosolic and nuclear RNA from human fetal and adult brain samples and performed a comprehensive analysis of cytosolic and nuclear transcriptomes. There are significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. We show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Differential expression analysis between fetal and adult frontal cortex show that results obtained from the cytosolic RNA differ from results using nuclear RNA both at the level of transcript types and the number of differentially expressed genes. Our data provide a resource for the subcellular localization of thousands of RNA transcripts in the human brain and highlight differences in using the cytosolic or the nuclear transcriptomes for expression analysis.

1 - 13 of 13
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf