A5036718218- Single-cell and spatial transcriptomics
- Zebrafish Biomedical Research Applications
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Platelet Disorders and Treatments
- Cell Image Analysis Techniques
- Epigenetics and DNA Methylation
- Immune cells in cancer
- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Aquaculture disease management and microbiota
- Gene expression and cancer classification
- DNA Repair Mechanisms
- IL-33, ST2, and ILC Pathways
- Digital Imaging for Blood Diseases
- Gene Regulatory Network Analysis
- Erythrocyte Function and Pathophysiology
- Blood Coagulation and Thrombosis Mechanisms
- Hemoglobinopathies and Related Disorders
- RNA Research and Splicing
- Prenatal Screening and Diagnostics
- Genetic Associations and Epidemiology
- Asthma and respiratory diseases
University of Copenhagen
2023-2025
University of Cambridge
2015-2024
Wellcome Sanger Institute
2014-2024
Wellcome/MRC Cambridge Stem Cell Institute
2015-2024
Medical Research Council
2015-2021
Wellcome Trust
2016-2019
Stem Cell Institute
2016-2019
Addenbrooke's Hospital
2017
Bridge University
2013
NHS Blood and Transplant
2011-2012
Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification new genetic lesions could facilitate diagnostic therapeutic strategies.We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome 9 patients with low-grade myelodysplasia. Targeted resequencing gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed cohort 2087 myeloid or other...
A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into many components our system, consortium examined regulation DNA and RNA transcription dissect molecular traits govern differentiation. By inducing responses, Saeed et al. document changes in genome underlie Cheng demonstrate trained monocytes are highly dependent on breakdown sugars presence oxygen, which allows produce energy needed mount an response. Chen examine transcripts...
Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development individual lineages. Here, we report genome-wide binding sites for five key hematopoietic transcription factors—GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL—in primary human megakaryocytes. Statistical analysis 17,263 regions bound by at least one factor demonstrated that simultaneous all factors was most enriched pattern often occurred near known regulators. Eight genes not...
Regulation of hematopoiesis during human development remains poorly defined. Here we applied single-cell RNA sequencing (scRNA-seq) and assay for transposase-accessible chromatin (scATAC-seq) to over 8,000 immunophenotypic blood cells from fetal liver bone marrow. We inferred their differentiation trajectory identified three highly proliferative oligopotent progenitor populations downstream hematopoietic stem (HSCs)/multipotent progenitors (MPPs). Along this trajectory, observed opposing...
The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature differentiation process. Here we applied single-cell RNA-sequencing to a population cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, were able place each cell along continuum from mature cell, refining...
Abstract Lung cancer is the second most frequently diagnosed and leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent have a well-established role promoting disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma squamous-cell carcinoma by single-cell spatial transcriptomics. We note an inverse relationship between anti-inflammatory...
Abstract DNA is subject to continual damage, leaving each cell with thousands of individual lesions at any given moment 1–3 . The efficiency repair means that most known classes lesion have a half-life minutes hours 3,4 , but the extent which damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising 818 persisted across multiple cycles in normal human stem cells blood, liver and bronchial epithelium...
Abstract The success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence well-defined cell surface markers specific diverse progenitor populations. An inherent problem with this approach that does not directly reflect transcriptional state a cell. Here, we used marker-free to computationally reconstruct blood lineage tree zebrafish order cells along their differentiation trajectory, based global differences. Within population...
Abstract CD4+ T cells are at the nexus of innate and adaptive arms immune system. However, little is known about evolutionary history cells, it unclear whether their differentiation into specialized subsets conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled allowing us to scrutinize development specialization teleost leukocytes vivo. We provide further evidence that macrophages an ancient origin had already emerged bony fish....
The immune system of vertebrate species consists many different cell types that have distinct functional roles and are subject to evolutionary pressures. Here, we first analyzed conservation genes specific for all major in human mouse. Our results revealed higher gene turnover faster evolution trans -membrane proteins NK cells compared with other types, especially T cells, but similar nuclear cytoplasmic protein coding genes. To validate these findings a distant species, used single-cell RNA...
Analyses of immune cells in rag1-deficient zebrafish led to the discovery innate lymphoid teleosts.
Wiskott-Aldrich syndrome protein (WASp) is haematopoietically restricted, and the causative underlying a severe human disorder that can lead to death due immunodeficiency haemorrhaging. Much known about biochemistry of WASp migratory capacity WASp-defective cells in vitro, but vivo studies immune-cell behaviour are more challenging. Using translucency zebrafish larvae, we live-imaged effects morpholino knockdown WASp1 (also as Was) on leukocyte migration response wound. In embryos at 22...
Abstract In this study, we demonstrate the suitability of vertebrate Danio rerio (zebrafish) for functional screening novel platelet genes in vivo by reverse genetics. Comparative transcript analysis platelets and their precursor cell, megakaryocyte, together with nucleated blood cell elements, endothelial cells, erythroblasts, identified membrane proteins hitherto unknown roles thrombus formation. We determined phenotype induced antisense morpholino oligonucleotide (MO)–based knockdown 5...
Abstract Background Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of embryo from a population haemogenic endothelial which undergo endothelial-to-haematopoietic transition (EHT). Despite progress achieved recent years, molecular mechanisms driving EHT are still poorly understood, especially human where AGM is not easily accessible. Results In this study, we take advantage pluripotent cell (hPSC) differentiation system and...
Abstract Background Single-cell RNA-sequencing is revolutionising the study of cellular and tissue-wide heterogeneity in a large number biological scenarios, from highly tissue-specific studies disease to human-wide cell atlases. A central task single-cell analysis design calculation type-specific genes order differential impact different replicates (e.g. tumour vs. non-tumour environment) on regulation those their associated networks. The crucial efficient reliable such ‘marker’ genes....
Down syndrome predisposes individuals to haematological abnormalities, such as increased number of erythrocytes and leukaemia in a process that is initiated before birth not entirely understood
Abstract Progressive dysfunction of mitochondria, organelles responsible for energy provision to cells, is a major hallmark ageing. How the steadily accrues over lifetime remains unclear, given transient nature free radical damage and high turnover mitochondria. Here, we leveraged whole-genome sequencing data from single-cell derived foetal adult haematopoietic stem/progenitor cell colonies study clonal dynamics selection in mitochondrial genomes throughout life. We found that genetic drift...