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  1. AU="Reinius, Björn"
  2. AU="Reis, L C"
  3. AU=Bonsignore M R
  4. AU="Millard, Glenda M"
  5. AU="Springer, Andrea"
  6. AU="Hyunho Han"
  7. AU="Grommen, Sylvia V H"
  8. AU="Asemani, Yahya"
  9. AU="Ketomäki, Tuomo"
  10. AU=Cavallini Giorgio
  11. AU="Saha, Aakash"
  12. AU="Noguchi, J"
  13. AU="Löhr, B."
  14. AU="Lokie, Kelsey B"

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  1. Artikel ; Online: Limitations of X:autosome ratio as a measurement of X-chromosome upregulation.

    Lentini, Antonio / Reinius, Björn

    Current biology : CB

    2023  Band 33, Heft 10, Seite(n) R395–R396

    Abstract: Lentini and Reinius address issues in interpreting non-allelic gene expression measurements of dosage compensation during murine embryonic development. ...

    Abstract Lentini and Reinius address issues in interpreting non-allelic gene expression measurements of dosage compensation during murine embryonic development.
    Mesh-Begriff(e) Female ; Pregnancy ; Animals ; Mice ; Up-Regulation ; X Chromosome ; Transcriptional Activation ; Dosage Compensation, Genetic ; Embryonic Development
    Sprache Englisch
    Erscheinungsdatum 2023-05-22
    Erscheinungsland England
    Dokumenttyp Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.03.059
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Monitoring of the SARS-CoV-2 Omicron BA.1/BA.2 lineage transition in the Swedish population reveals increased viral RNA levels in BA.2 cases.

    Lentini, Antonio / Pereira, Antonio / Winqvist, Ola / Reinius, Björn

    Med (New York, N.Y.)

    2022  Band 3, Heft 9, Seite(n) 636–643.e4

    Abstract: Background: Throughout the SARS-CoV-2 pandemic, multiple waves of variants of concern have swept across populations, leading to a chain of new and yet more contagious variants dominating COVID-19 cases. Here, we tracked the remarkably rapid shift from ... ...

    Abstract Background: Throughout the SARS-CoV-2 pandemic, multiple waves of variants of concern have swept across populations, leading to a chain of new and yet more contagious variants dominating COVID-19 cases. Here, we tracked the remarkably rapid shift from Omicron BA.1 to BA.2 sublineage dominance in the Swedish population in early 2022 at a day-by-day basis.
    Methods: Using a custom SARS-CoV-2 Omicron BA.1 lineage-typing RT-PCR assay, we analyzed 174,933 clinical upper airway samples collected during January to March 2022.
    Findings: Our study demonstrates the feasibility and reliability of parallel lineage assignment of select variants at population scale, tracking the dominant sublineage transition from BA.1 to BA.2 at day-to-day resolution and uncovering nearly 2-fold higher levels of viral RNA in cases infected with Omicron BA.2 relative to BA.1.
    Conclusions: Our data provide unique insights into the Omicron BA.1 to BA.2 transition that occurred in Sweden during early 2022, and later, across the world. This may help to understand the increased transmissibility of the BA.2 variant.
    Mesh-Begriff(e) COVID-19/epidemiology ; Humans ; RNA, Viral/genetics ; Reproducibility of Results ; SARS-CoV-2/genetics ; Sweden/epidemiology
    Chemische Substanzen RNA, Viral
    Sprache Englisch
    Erscheinungsdatum 2022-08-08
    Erscheinungsland United States
    Dokumenttyp Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2022.07.007
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  3. Artikel ; Online: Voltage-Seq: all-optical postsynaptic connectome-guided single-cell transcriptomics.

    Csillag, Veronika / Bizzozzero, Marianne Hiriart / Noble, J C / Reinius, Björn / Fuzik, János

    Nature methods

    2023  Band 20, Heft 9, Seite(n) 1409–1416

    Abstract: Understanding the routing of neuronal information requires the functional characterization of connections. Neuronal projections recruit large postsynaptic ensembles with distinct postsynaptic response types (PRTs). PRT is typically probed by low- ... ...

    Abstract Understanding the routing of neuronal information requires the functional characterization of connections. Neuronal projections recruit large postsynaptic ensembles with distinct postsynaptic response types (PRTs). PRT is typically probed by low-throughput whole-cell electrophysiology and is not a selection criterion for single-cell RNA-sequencing (scRNA-seq). To overcome these limitations and target neurons based on specific PRTs for soma harvesting and subsequent scRNA-seq, we created Voltage-Seq. We established all-optical voltage imaging and recorded the PRT of 8,347 neurons in the mouse periaqueductal gray (PAG) evoked by the optogenetic activation of ventromedial hypothalamic (VMH) terminals. PRTs were classified and spatially resolved in the entire VMH-PAG connectome. We built an onsite analysis tool named VoltView to navigate soma harvesting towards target PRTs guided by a classifier that used the VMH-PAG connectome database as a reference. We demonstrated Voltage-seq by locating VMH-driven γ-aminobutyric acid-ergic neurons in the PAG, guided solely by the onsite classification in VoltView.
    Mesh-Begriff(e) Mice ; Animals ; Connectome ; Transcriptome ; Neurons/physiology ; Periaqueductal Gray/physiology
    Sprache Englisch
    Erscheinungsdatum 2023-07-20
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-023-01965-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Monitoring of the SARS-CoV-2 Omicron BA.1/BA.2 variant transition in the Swedish population reveals higher viral quantity in BA.2 cases

    Lentini, Antonio / Pereira, Antonio / Winqvist, Ola / Reinius, Björn

    medRxiv

    Abstract: Throughout the SARS-CoV-2 pandemic, multiple waves of variants of concern have swept across populations, leading to a chain of new and yet more contagious lineages dominating COVID-19 cases. Here, we tracked the remarkably rapid shift from Omicron BA.1 ... ...

    Abstract Throughout the SARS-CoV-2 pandemic, multiple waves of variants of concern have swept across populations, leading to a chain of new and yet more contagious lineages dominating COVID-19 cases. Here, we tracked the remarkably rapid shift from Omicron BA.1 to BA.2 sub-variant dominance in the Swedish population during January-March 2022. By analysis of 174,933 clinical nasopharyngeal swab samples using a custom variant-typing RT-PCR assay, we uncover nearly two-fold higher levels of viral RNA in cases with Omicron BA.2. Importantly, increased viral load in the upper pharynx upon BA.2 infection may provide part of the explanation why Omicron BA.2 is more transmissible and currently outcompetes the BA.1 variant across populations.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2022-03-27
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2022.03.26.22272984
    Datenquelle COVID19

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  5. Artikel ; Online: Reply to 'High prevalence of clonal monoallelic expression'.

    Reinius, Björn / Sandberg, Rickard

    Nature genetics

    2018  Band 50, Heft 9, Seite(n) 1199–1200

    Mesh-Begriff(e) Alleles ; Gene Expression ; Immune System ; Prevalence
    Sprache Englisch
    Erscheinungsdatum 2018-08-03
    Erscheinungsland United States
    Dokumenttyp Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-018-0189-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force.

    Smyrlaki, Ioanna / Fördős, Ferenc / Rocamonde-Lago, Iris / Wang, Yang / Shen, Boxuan / Lentini, Antonio / Luca, Vincent C / Reinius, Björn / Teixeira, Ana I / Högberg, Björn

    Nature communications

    2024  Band 15, Heft 1, Seite(n) 465

    Abstract: The Notch signaling pathway has fundamental roles in embryonic development and in the nervous system. The current model of receptor activation involves initiation via a force-induced conformational change. Here, we define conditions that reveal pulling ... ...

    Abstract The Notch signaling pathway has fundamental roles in embryonic development and in the nervous system. The current model of receptor activation involves initiation via a force-induced conformational change. Here, we define conditions that reveal pulling force-independent Notch activation using soluble multivalent constructs. We treat neuroepithelial stem-like cells with molecularly precise ligand nanopatterns displayed from solution using DNA origami. Notch signaling follows with clusters of Jag1, and with chimeric structures where most Jag1 proteins are replaced by other binders not targeting Notch. Our data rule out several confounding factors and suggest a model where Jag1 activates Notch upon prolonged binding without appearing to need a pulling force. These findings reveal a distinct mode of activation of Notch and lay the foundation for the development of soluble agonists.
    Mesh-Begriff(e) Receptors, Notch/metabolism ; Jagged-1 Protein/genetics ; Jagged-1 Protein/metabolism ; Signal Transduction/physiology ; Calcium-Binding Proteins/metabolism
    Chemische Substanzen Receptors, Notch ; Jagged-1 Protein ; Calcium-Binding Proteins
    Sprache Englisch
    Erscheinungsdatum 2024-01-18
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44059-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Elastic dosage compensation by X-chromosome upregulation.

    Lentini, Antonio / Cheng, Huaitao / Noble, J C / Papanicolaou, Natali / Coucoravas, Christos / Andrews, Nathanael / Deng, Qiaolin / Enge, Martin / Reinius, Björn

    Nature communications

    2022  Band 13, Heft 1, Seite(n) 1854

    Abstract: X-chromosome inactivation and X-upregulation are the fundamental modes of chromosome-wide gene regulation that collectively achieve dosage compensation in mammals, but the regulatory link between the two remains elusive and the X-upregulation dynamics ... ...

    Abstract X-chromosome inactivation and X-upregulation are the fundamental modes of chromosome-wide gene regulation that collectively achieve dosage compensation in mammals, but the regulatory link between the two remains elusive and the X-upregulation dynamics are unknown. Here, we use allele-resolved single-cell RNA-seq combined with chromatin accessibility profiling and finely dissect their separate effects on RNA levels during mouse development. Surprisingly, we uncover that X-upregulation elastically tunes expression dosage in a sex- and lineage-specific manner, and moreover along varying degrees of X-inactivation progression. Male blastomeres achieve X-upregulation upon zygotic genome activation while females experience two distinct waves of upregulation, upon imprinted and random X-inactivation; and ablation of Xist impedes female X-upregulation. Female cells carrying two active X chromosomes lack upregulation, yet their collective RNA output exceeds that of a single hyperactive allele. Importantly, this conflicts the conventional dosage compensation model in which naïve female cells are initially subject to biallelic X-upregulation followed by X-inactivation of one allele to correct the X dosage. Together, our study provides key insights to the chain of events of dosage compensation, explaining how transcript copy numbers can remain remarkably stable across developmental windows wherein severe dose imbalance would otherwise be experienced by the cell.
    Mesh-Begriff(e) Alleles ; Animals ; Dosage Compensation, Genetic ; Female ; Male ; Mammals/genetics ; Mice ; RNA, Long Noncoding/genetics ; Up-Regulation ; X Chromosome/genetics ; X Chromosome Inactivation/genetics
    Chemische Substanzen RNA, Long Noncoding
    Sprache Englisch
    Erscheinungsdatum 2022-04-06
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29414-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Transcriptional kinetics and molecular functions of long noncoding RNAs.

    Johnsson, Per / Ziegenhain, Christoph / Hartmanis, Leonard / Hendriks, Gert-Jan / Hagemann-Jensen, Michael / Reinius, Björn / Sandberg, Rickard

    Nature genetics

    2022  Band 54, Heft 3, Seite(n) 306–317

    Abstract: An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single- ... ...

    Abstract An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared to messenger RNAs, lncRNAs have twice as long duration between two transcriptional bursts. Additionally, we observed increased cell-to-cell variability in lncRNA expression due to lower frequency bursting producing larger numbers of RNA molecules. Exploiting heterogeneity in asynchronously growing cells, we identified and experimentally validated lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis. Finally, we identified cis-functioning lncRNAs and showed that knockdown of these lncRNAs modulated the nearby protein-coding gene's transcriptional burst frequency or size. In summary, we identified distinct transcriptional regulation of lncRNAs and demonstrated a role for lncRNAs in the regulation of mRNA transcriptional bursting.
    Mesh-Begriff(e) Gene Expression Regulation/genetics ; Kinetics ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcription, Genetic/genetics
    Chemische Substanzen RNA, Long Noncoding ; RNA, Messenger
    Sprache Englisch
    Erscheinungsdatum 2022-03-03
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-022-01014-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Random monoallelic expression of autosomal genes: stochastic transcription and allele-level regulation.

    Reinius, Björn / Sandberg, Rickard

    Nature reviews. Genetics

    2015  Band 16, Heft 11, Seite(n) 653–664

    Abstract: Random monoallelic expression (RME) of genes represents a striking example of how stochastic molecular processes can result in cellular heterogeneity. Recent transcriptome-wide studies have revealed both mitotically stable and cell-to-cell dynamic forms ... ...

    Abstract Random monoallelic expression (RME) of genes represents a striking example of how stochastic molecular processes can result in cellular heterogeneity. Recent transcriptome-wide studies have revealed both mitotically stable and cell-to-cell dynamic forms of autosomal RME, with the latter presumably resulting from burst-like stochastic transcription. Here, we discuss the distinguishing features of these two forms of RME and revisit literature on their nature, pervasiveness and regulation. Finally, we explore how RME may contribute to phenotypic variation, including the incomplete penetrance and variable expressivity often seen in genetic disease.
    Mesh-Begriff(e) Alleles ; Gene Expression Profiling/methods ; Genetic Association Studies/methods ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Models, Genetic ; Phenotype ; Stochastic Processes ; Transcriptome/genetics
    Sprache Englisch
    Erscheinungsdatum 2015-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/nrg3888
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  10. Artikel ; Online: X-chromosome upregulation is driven by increased burst frequency.

    Larsson, Anton J M / Coucoravas, Christos / Sandberg, Rickard / Reinius, Björn

    Nature structural & molecular biology

    2019  Band 26, Heft 10, Seite(n) 963–969

    Abstract: Ohno's hypothesis postulates that upregulation of X-linked genes rectifies their dosage imbalance relative to autosomal genes, which are present in two active copies per cell. Here we have dissected X-chromosome upregulation into the kinetics of ... ...

    Abstract Ohno's hypothesis postulates that upregulation of X-linked genes rectifies their dosage imbalance relative to autosomal genes, which are present in two active copies per cell. Here we have dissected X-chromosome upregulation into the kinetics of transcription, inferred from allele-specific single-cell RNA sequencing data from somatic and embryonic mouse cells. We confirmed increased X-chromosome expression levels in female and male cells and found that the X chromosome achieved upregulation by elevated burst frequencies. By monitoring transcriptional kinetics in differentiating female mouse embryonic stem cells, we found that increased burst frequency was established on the active X chromosome when X inactivation took place on the other allele. Thus, our study provides mechanistic insights into X-chromosome upregulation.
    Mesh-Begriff(e) Alleles ; Animals ; Cells, Cultured ; Female ; Gene Expression Regulation, Developmental ; Genes, X-Linked ; Male ; Mice ; Mice, Inbred C57BL ; Transcriptional Activation ; Up-Regulation ; X Chromosome/genetics ; X Chromosome Inactivation
    Sprache Englisch
    Erscheinungsdatum 2019-10-03
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-019-0306-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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