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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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- Chen, DS, et al.
(författare)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Tidskriftsartikel (refereegranskat)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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- Bakken, TE, et al.
(författare)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Tidskriftsartikel (refereegranskat)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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- Zhang, XN, et al.
(författare)
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An update on viral association of human cancers
- 2013
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Ingår i: Archives of virology. - : Springer Science and Business Media LLC. - 1432-8798 .- 0304-8608. ; 158:7, s. 1433-1443
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Bai, XN, et al.
(författare)
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Molecular Characterization and Comparative Genomics of Clinical Hybrid Shiga Toxin-Producing and Enterotoxigenic Escherichia coli (STEC/ETEC) Strains in Sweden
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 5619-
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid E. coli pathotypes are representing emerging public health threats with enhanced virulence from different pathotypes. Hybrids of Shiga toxin-producing and enterotoxigenic E. coli (STEC/ETEC) have been reported to be associated with diarrheal disease and hemolytic uremic syndrome (HUS) in humans. Here, we identified and characterized four clinical STEC/ETEC hybrids from diarrheal patients with or without fever or abdominal pain and healthy contact in Sweden. Rare stx2 subtypes were present in STEC/ETEC hybrids. Stx2 production was detectable in stx2a and stx2e containing strains. Different copies of ETEC virulence marker, sta gene, were found in two hybrids. Three sta subtypes, namely, sta1, sta4 and sta5 were designated, with sta4 being predominant. The hybrids represented diverse and rare serotypes (O15:H16, O187:H28, O100:H30, and O136:H12). Genome-wide phylogeny revealed that these hybrids exhibited close relatedness with certain ETEC, STEC/ETEC hybrid and commensal E. coli strains, implying the potential acquisition of Stx-phages or/and ETEC virulence genes in the emergence of STEC/ETEC hybrids. Given the emergence and public health significance of hybrid pathotypes, a broader range of virulence markers should be considered in the E. coli pathotypes diagnostics, and targeted follow up of cases is suggested to better understand the hybrid infection.
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| 21. |
- Pan, YY, et al.
(författare)
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Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals
- 2021
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Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Non-O157 Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause zoonotic diseases. To investigate the antimicrobial resistance of STEC in China, non-O157 STEC isolates, recovered from domestic animals and humans from 12 provinces, were analyzed using antimicrobial susceptibility testing and whole genome characterization. Out of the 298 isolates tested, 115 strains showed resistance to at least one antimicrobial and 85 strains showed multidrug resistance. The highest resistance rate was to tetracycline (32.6%), followed by nalidixic acid (25.2%) and chloramphenicol and azithromycin (both 18.8%). However, imipenem and meropenem were effective against all isolates. Antimicrobial resistance patterns varied among strains from different sources. Strains from pig, sheep, humans, and cattle showed resistance rates of 100.0%, 46.9%, 30.3%, and 6.3% to one or more antimicrobials, respectively. Forty-three genes related to 11 antimicrobial classes were identified among these strains. The colistin-resistance gene mcr was only carried by strains from pigs. A new fosfomycin-resistant gene, fosA7, was detected in strains from humans, cattle, and sheep. Whole genome phylogenetic analysis showed that strains from the four sources were genetically diverse and scattered throughout the phylogenetic tree; however, some strains from the same source had a tendency to cluster closely. These results provide a reference to monitor the emergence and spread of multidrug resistant STEC strains among animals and humans. Furthermore, with a better understanding of antimicrobial genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary.
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| 22. |
- Shah, MY, et al.
(författare)
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Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
- 2018
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 28:4, s. 432-447
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Tidskriftsartikel (refereegranskat)abstract
- The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
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| 27. |
- Yang, X, et al.
(författare)
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Genetic diversity of the intimin gene (eae) in non-O157 Shiga toxin-producing Escherichia coli strains in China
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 3275-
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Tidskriftsartikel (refereegranskat)abstract
- Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen. The increasing incidence of non-O157 STEC has posed a great risk to public health. Besides the Shiga toxin (Stx), the adherence factor, intimin, coded by eae gene plays a critical role in STEC pathogenesis. In this study, we investigated the prevalence and polymorphisms of eae gene in non-O157 STEC strains isolated from different sources in China. Among 735 non-O157 STEC strains, eae was present in 70 (9.5%) strains. Eighteen different eae genotypes were identified in 62 eae-positive STEC strains with the nucleotide identities ranging from 86.01% to 99.97%. Among which, seven genotypes were newly identified in this study. The eighteen eae genotypes can be categorized into five eae subtypes, namely β1, γ1, ε1, ζ3 and θ. Associations between eae subtypes/genotypes and serotypes as well as origins of strains were observed in this study. Strains belonging to serotypes O26:H11, O103:H2, O111:H8 are associated with particular eae subtypes, i.e., β1, ε1, θ, respectively. Most strains from diarrheal patients (7/9, 77.8%) carried eae-β1 subtype, while most isolates from cattle (23/26, 88.5%) carried eae-ζ3 subtype. This study demonstrated a genetic diversity of eae gene in non-O157 STEC strains from different sources in China.
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| 32. |
- Zhang, XY, et al.
(författare)
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Preventive strategies of cancer therapeutics-related cardiotoxicity in childhood cancer survivors: a protocol of systematic review
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e065776-
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Tidskriftsartikel (refereegranskat)abstract
- Five-year survival in childhood cancer has been improved markedly in the past decades. Childhood cancer survivors are at high risk of cardiovascular diseases due to anticancer therapy-induced cardiotoxicity. The comprehensive evidence for the prevention of anticancer therapy-induced cardiovascular disease is, however, sparse. The systematic review described in the protocol aims to summarise the effect of current prevention for anticancer therapy-induced cardiotoxicity among childhood cancer survivors.Methods and analysisThis protocol is reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. We will search PubMed (via Medline), Embase and the Cochrane Library and include the studies investigating the effect of prevention against anticancer therapy-induced cardiotoxicity of childhood cancer. To assess the risk of bias, we will use the Cochrane Collaboration’s risk of bias tool for randomised control trials and the Newcastle-Ottawa Scale for cohort studies and case–control studies. Furthermore, we will conduct meta-analyses if there is no substantial clinical heterogeneity between included studies. The Grading of Recommendations, Assessment, Development and Evaluation will be used to evaluate the quality of evidence.Ethics and disseminationEthical approval is not needed for systematic review of published data. The findings will be published in a peer-reviewed journal and disseminated at scientific conferences.PROSPERO registration numberCRD42022333877.
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