{"entity": "researcher", "timestamp": "2026-07-17T08:41:51.617Z", "family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "affiliations": ["Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732"}}, "publications": [{"entity": "publication", "iuid": "d6a88ec152fc41aa9cd664708fc3c565", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d6a88ec152fc41aa9cd664708fc3c565.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d6a88ec152fc41aa9cd664708fc3c565"}}, "title": "A combined approach for single-cell mRNA and intracellular protein expression analysis.", "authors": [{"family": "Reimeg\u00e5rd", "given": "Johan", "initials": "J"}, {"family": "Tarbier", "given": "Marcel", "initials": "M"}, {"family": "Danielsson", "given": "Marcus", "initials": "M", "orcid": "0000-0003-4418-0165", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6b237ce613e4ef8a6d7ab2654c2c41e.json"}}, {"family": "Schuster", "given": "Jens", "initials": "J", "orcid": "0000-0002-4383-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/a194d037b21c47a2926b082e9e79de31.json"}}, {"family": "Baskaran", "given": "Sathishkumar", "initials": "S"}, {"family": "Panagiotou", "given": "Styliani", "initials": "S"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}, {"family": "Friedl\u00e4nder", "given": "Marc R", "initials": "MR"}, {"family": "Gallant", "given": "Caroline J", "initials": "CJ", "orcid": "0000-0002-1499-8444", "researcher": {"href": "https://publications.scilifelab.se/researcher/b11c1c853309426faed0af716f1288cd.json"}}], "type": "journal article", "published": "2021-05-25", "journal": {"title": "Commun Biol", "issn": "2399-3642", "issn-l": "2399-3642", "volume": "4", "issue": "1", "pages": "624"}, "abstract": "Combined measurements of mRNA and protein expression in single cells enable in-depth analysis of cellular states. We present SPARC, an approach that combines single-cell RNA-sequencing with proximity extension essays to simultaneously measure global mRNA and 89 intracellular proteins in individual cells. We show that mRNA expression fails to accurately reflect protein abundance at the time of measurement, although the direction of changes is in agreement during neuronal differentiation. Moreover, protein levels of transcription factors better predict their downstream effects than do their corresponding transcripts. Finally, we highlight that protein expression variation is overall lower than mRNA variation, but relative protein variation does not reflect the mRNA level. Our results demonstrate that mRNA and protein measurements in single cells provide different and complementary information regarding cell states. SPARC presents a state-of-the-art co-profiling method that overcomes current limitations in throughput and protein localization, including removing the need for cell fixation.", "doi": "10.1038/s42003-021-02142-w", "pmid": "34035432", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Affinity Proteomics Uppsala": "Technology development", "National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-021-02142-w"}, {"db": "pmc", "key": "PMC8149646"}], "notes": [], "created": "2021-06-02T12:38:48.106Z", "modified": "2024-01-16T13:48:39.677Z"}, {"entity": "publication", "iuid": "61cb2c382f5b4954ae79250a61c45daa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/61cb2c382f5b4954ae79250a61c45daa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/61cb2c382f5b4954ae79250a61c45daa"}}, "title": "DNA methylation changes in Down syndrome derived neural iPSCs uncover co-dysregulation of ZNF and HOX3 families of transcription factors.", "authors": [{"family": "Laan", "given": "Loora", "initials": "L"}, {"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Hoeber", "given": "Jan", "initials": "J"}, {"family": "Shahsavani", "given": "Mansoureh", "initials": "M"}, {"family": "Kele", "given": "Malin", "initials": "M"}, {"family": "Fatima", "given": "Ambrin", "initials": "A"}, {"family": "Zakaria", "given": "Muhammad", "initials": "M"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Falk", "given": "Anna", "initials": "A"}, {"family": "Schuster", "given": "Jens", "initials": "J"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}], "type": "comparative study", "published": "2020-01-08", "journal": {"volume": "12", "issn": "1868-7083", "issue": "1", "pages": "9", "title": "Clin Epigenetics", "issn-l": "1868-7075"}, "abstract": "Down syndrome (DS) is characterized by neurodevelopmental abnormalities caused by partial or complete trisomy of human chromosome 21 (T21). Analysis of Down syndrome brain specimens has shown global epigenetic and transcriptional changes but their interplay during early neurogenesis remains largely unknown. We differentiated induced pluripotent stem cells (iPSCs) established from two DS patients with complete T21 and matched euploid donors into two distinct neural stages corresponding to early- and mid-gestational ages.\n\nUsing the Illumina Infinium 450K array, we assessed the DNA methylation pattern of known CpG regions and promoters across the genome in trisomic neural iPSC derivatives, and we identified a total of 500 stably and differentially methylated CpGs that were annotated to CpG islands of 151 genes. The genes were enriched within the DNA binding category, uncovering 37 factors of importance for transcriptional regulation and chromatin structure. In particular, we observed regional epigenetic changes of the transcription factor genes ZNF69, ZNF700 and ZNF763 as well as the HOXA3, HOXB3 and HOXD3 genes. A similar clustering of differential methylation was found in the CpG islands of the HIST1 genes suggesting effects on chromatin remodeling.\n\nThe study shows that early established differential methylation in neural iPSC derivatives with T21 are associated with a set of genes relevant for DS brain development, providing a novel framework for further studies on epigenetic changes and transcriptional dysregulation during T21 neurogenesis.", "doi": "10.1186/s13148-019-0803-1", "pmid": "31915063", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Long-term Support WABI": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13148-019-0803-1"}, {"db": "pmc", "key": "PMC6950999"}], "notes": [], "created": "2020-01-14T10:04:59.643Z", "modified": "2021-11-10T12:55:02.672Z"}, {"entity": "publication", "iuid": "1a1d372b9e16494cbd68b5793f731edf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1a1d372b9e16494cbd68b5793f731edf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1a1d372b9e16494cbd68b5793f731edf"}}, "title": "Transcriptomes of Dravet syndrome iPSC derived GABAergic cells reveal dysregulated pathways for chromatin remodeling and neurodevelopment.", "authors": [{"family": "Schuster", "given": "Jens", "initials": "J", "orcid": "0000-0002-4383-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/a194d037b21c47a2926b082e9e79de31.json"}}, {"family": "Laan", "given": "Loora", "initials": "L"}, {"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Jin", "given": "Zhe", "initials": "Z"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Korol", "given": "Sergiy", "initials": "S"}, {"family": "Noraddin", "given": "Feria Hikmet", "initials": "FH"}, {"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Birnir", "given": "Bryndis", "initials": "B"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}], "type": "journal article", "published": "2019-12-00", "journal": {"volume": "132", "issn": "1095-953X", "issue": null, "pages": "104583", "title": "Neurobiol. Dis.", "issn-l": "0969-9961"}, "abstract": "Dravet syndrome (DS) is an early onset refractory epilepsy typically caused by de novo heterozygous variants in SCN1A encoding the \u03b1-subunit of the neuronal sodium channel Na v1.1. The syndrome is characterized by age-related progression of seizures, cognitive decline and movement disorders. We hypothesized that the distinct neurodevelopmental features in DS are caused by the disruption of molecular pathways in Nav1.1 haploinsufficient cells resulting in perturbed neural differentiation and maturation. Here, we established DS-patient and control induced pluripotent stem cell derived neural progenitor cells (iPSC NPC) and GABAergic inter-neuronal (iPSC GABA) cells. The DS-patient iPSC GABA cells showed a shift in sodium current activation and a perturbed response to induced oxidative stress. Transcriptome analysis revealed specific dysregulations of genes for chromatin structure, mitotic progression, neural plasticity and excitability in DS-patient iPSC NPCs and DS-patient iPSC GABA cells versus controls. The transcription factors FOXM1 and E2F1, positive regulators of the disrupted pathways for histone modification and cell cycle regulation, were markedly up-regulated in DS-iPSC GABA lines. Our study highlights transcriptional changes and disrupted pathways of chromatin remodeling in Nav1.1 haploinsufficient GABAergic cells, providing a molecular framework that overlaps with that of neurodevelopmental disorders and other epilepsies.", "doi": "10.1016/j.nbd.2019.104583", "pmid": "31445158", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0969-9961(19)30251-7"}], "notes": [], "created": "2019-11-20T15:33:02.190Z", "modified": "2024-01-16T13:48:43.380Z"}, {"entity": "publication", "iuid": "896c9ba71a5a4bc8a9a93699bd1f5df7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/896c9ba71a5a4bc8a9a93699bd1f5df7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/896c9ba71a5a4bc8a9a93699bd1f5df7"}}, "title": "Transcriptome and Proteome Profiling of Neural Induced Pluripotent Stem Cells from Individuals with Down Syndrome Disclose Dynamic Dysregulations of Key Pathways and Cellular Functions.", "authors": [{"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Laan", "given": "Loora", "initials": "L"}, {"family": "Shahsavani", "given": "Mansoureh", "initials": "M"}, {"family": "Schuster", "given": "Jens", "initials": "J"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Konzer", "given": "Anne", "initials": "A"}, {"family": "Mi", "given": "Jia", "initials": "J"}, {"family": "Bergquist", "given": "Jonas", "initials": "J"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Hoeber", "given": "Jan", "initials": "J"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Falk", "given": "Anna", "initials": "A"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}], "type": "journal article", "published": "2019-10-00", "journal": {"volume": "56", "issn": "1559-1182", "issue": "10", "pages": "7113-7127", "title": "Mol Neurobiol", "issn-l": "0893-7648"}, "abstract": "Down syndrome (DS) or trisomy 21 (T21) is a leading genetic cause of intellectual disability. To gain insights into dynamics of molecular perturbations during neurogenesis in DS, we established a model using induced pluripotent stem cells (iPSC) with transcriptome profiles comparable to that of normal fetal brain development. When applied on iPSCs with T21, transcriptome and proteome signatures at two stages of differentiation revealed strong temporal dynamics of dysregulated genes, proteins and pathways belonging to 11 major functional clusters. DNA replication, synaptic maturation and neuroactive clusters were disturbed at the early differentiation time point accompanied by a skewed transition from the neural progenitor cell stage and reduced cellular growth. With differentiation, growth factor and extracellular matrix, oxidative phosphorylation and glycolysis emerged as major perturbed clusters. Furthermore, we identified a marked dysregulation of a set of genes encoded by chromosome 21 including an early upregulation of the hub gene APP, supporting its role for disturbed neurogenesis, and the transcription factors OLIG1, OLIG2 and RUNX1, consistent with deficient myelination and neuronal differentiation. Taken together, our findings highlight novel sequential and differentiation-dependent dynamics of disturbed functions, pathways and elements in T21 neurogenesis, providing further insights into developmental abnormalities of the DS brain.", "doi": "10.1007/s12035-019-1585-3", "pmid": "30989628", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1007/s12035-019-1585-3"}, {"db": "pmc", "key": "PMC6728280"}], "notes": [], "created": "2019-05-03T06:15:57.377Z", "modified": "2024-01-16T13:48:43.744Z"}, {"entity": "publication", "iuid": "b4d4451c7e4b49bca2ca64e753e5cf5c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4d4451c7e4b49bca2ca64e753e5cf5c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4d4451c7e4b49bca2ca64e753e5cf5c"}}, "title": "Detailed analysis of HTT repeat elements in human blood using targeted amplification-free long-read sequencing.", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Tsai", "given": "Yu-Chih", "initials": "YC"}, {"family": "Clark", "given": "Tyson A", "initials": "TA"}, {"family": "Kotturi", "given": "Paul", "initials": "P"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2018-09-00", "journal": {"volume": "39", "issn": "1098-1004", "issue": "9", "pages": "1262-1272", "title": "Hum. Mutat.", "issn-l": "1059-7794"}, "abstract": "Amplification of DNA is required as a mandatory step during library preparation in most targeted sequencing protocols. This can be a critical limitation when targeting regions that are highly repetitive or with extreme guanine-cytosine (GC) content, including repeat expansions associated with human disease. Here, we used an amplification-free protocol for targeted enrichment utilizing the CRISPR/Cas9 system (No-Amp Targeted sequencing) in combination with single molecule, real-time (SMRT) sequencing for studying repeat elements in the huntingtin (HTT) gene, where an expanded CAG repeat is causative for Huntington disease. We also developed a robust data analysis pipeline for repeat element analysis that is independent of alignment of reads to a reference genome. The method was applied to 11 diagnostic blood samples, and for all 22 alleles the resulting CAG repeat count agreed with previous results based on fragment analysis. The amplification-free protocol also allowed for studying somatic variability of repeat elements in our samples, without the interference of PCR stutter. In summary, with No-Amp Targeted sequencing in combination with our analysis pipeline, we could accurately study repeat elements that are difficult to investigate using PCR-based methods.", "doi": "10.1002/humu.23580", "pmid": "29932473", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6175010"}], "notes": [], "created": "2018-10-15T09:36:08.234Z", "modified": "2024-01-16T13:48:45.682Z"}]}