A5082711932- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mesenchymal stem cell research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Chronic Myeloid Leukemia Treatments
- Multiple Myeloma Research and Treatments
- T-cell and B-cell Immunology
- Eosinophilic Disorders and Syndromes
- CAR-T cell therapy research
- Digital Imaging for Blood Diseases
- Invertebrate Immune Response Mechanisms
- Physiological and biochemical adaptations
- Pancreatic function and diabetes
- Erythrocyte Function and Pathophysiology
- Advanced Biosensing Techniques and Applications
- Kruppel-like factors research
- Virus-based gene therapy research
- Chemokine receptors and signaling
- Pluripotent Stem Cells Research
- Zebrafish Biomedical Research Applications
Wellcome/MRC Cambridge Stem Cell Institute
2016-2024
University of Cambridge
2016-2024
Stem Cell Institute
2017-2019
Medical Research Council
2016-2018
Wellcome Trust
2017
Abstract The lymphocyte genome is prone to many threats, including programmed mutation during differentiation 1 , antigen-driven proliferation and residency in diverse microenvironments. Here, after developing protocols for expansion of single-cell cultures, we sequenced whole genomes from 717 normal naive memory B T cells haematopoietic stem cells. All subsets carried more point mutations structural variants than cells, with higher burdens accumulating at a rate throughout life. Off-target...
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Despite rapid advances in mapping genetic drivers and gene expression changes hematopoietic stem cells (HSCs), there is a relative paucity of studies at the protein level. Here, we perform deep, multi-omic characterization (epigenome, transcriptome proteome) HSCs carrying loss-of-function mutation Tet2, key driver increased self-renewal blood cancers. Using state-of-the-art, multiplexed, low-input mass spectrometry (MS)-based proteomics, profile wildtype (WT) TET2-deficient (Tet2-/-) show...
Advances in the isolation and gene expression profiling of single hematopoietic stem cells (HSCs) have permitted in-depth resolution their molecular program. However, long-term HSCs can only be isolated to near purity from adult mouse bone marrow, thereby precluding studies program different physiological states. Here, we describe a powerful 7-day HSC hibernation culture system that maintains as absence physical niche. Single hibernating retain full functional potential compared with freshly...
Acute myeloid leukemia (AML) and neoplasms develop through acquisition of somatic mutations that confer mutation-specific fitness advantages to hematopoietic stem progenitor cells. However, our understanding mutational effects remains limited the resolution attainable within immunophenotypically clinically accessible bulk cell populations. To decipher heterogeneous cellular preleukemic perturbations, we performed single-cell RNA sequencing eight different mouse models with driver...
Key studies in pre-leukemic disorders have linked increases pro-inflammatory cytokines with accelerated phases of the disease, but precise role cellular microenvironment disease initiation and evolution remains poorly understood. In myeloproliferative neoplasms (MPNs), higher levels specific been previously correlated increased severity (tumor necrosis factor-alpha [TNF-α], interferon gamma-induced protein-10 [IP-10 or CXCL10]) decreased survival (interleukin 8 [IL-8]). Whereas TNF-α IL-8...
Abstract A lymphocyte suffers many threats to its genome, including programmed mutation during differentiation, antigen-driven proliferation and residency in diverse microenvironments. After developing protocols for single-cell expansions, we sequenced whole genomes from 717 normal naive memory B T lymphocytes hematopoietic stem cells. Lymphocytes carried more point mutations structural variation than cells, accruing at higher rates attributable both exogenous endogenous mutational...
Summary Hematopoietic stem cells (HSCs) cultured outside the body are fundamental component of a wide range cellular and gene therapies. Recent efforts have achieved more than 200-fold expansion functional HSCs, but their molecular characterization has not been possible due to substantial majority being non-HSCs single cell-initiated cultures displaying clone-to-clone variability. Using Fgd5 reporter mouse in combination with EPCR surface marker, we report exclusive identification HSCs from...