A5045213108- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Immune cells in cancer
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Renal and related cancers
- RNA and protein synthesis mechanisms
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Phagocytosis and Immune Regulation
- Mesenchymal stem cell research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Zebrafish Biomedical Research Applications
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Extracellular vesicles in disease
- Antimicrobial Peptides and Activities
Harvard University Press
2025
Massachusetts General Hospital
2022-2025
Harvard Stem Cell Institute
2022-2024
Harvard University
2022-2024
Stem Cell Institute
2024
Lund University
2016-2023
Institute for Stem Cell Biology and Regenerative Medicine
2018
Novo Nordisk Foundation
2015
University of Copenhagen
2015
Norwegian Defence Research Establishment
1981
Article2 June 2015Open Access Systems-wide analysis of BCR signalosomes and downstream phosphorylation ubiquitylation Shankha Satpathy Department Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty Health Medical Sciences, University Copenhagen, Denmark Search more papers by this author Sebastian A Wagner Petra Beli Rajat Gupta Trine Kristiansen Dessislava Malinova Division Immune Cell Biology, MRC National Institute Mill Hill, London, UK Chiara Francavilla Pavel...
A hallmark of adult hematopoiesis is the continuous replacement blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage foundation clinical HSC transplantation, recent reports have questioned physiological HSCs normal/steady-state hematopoiesis. Here, we use inducible lineage tracing from genetically marked and reveal robust HSC-derived This commences via defined progenitor cells, but varies substantially in between different lineages. By...
The adult immune system consists of cells that emerged at various times during ontogeny. We aimed to define the relationship between developmental origin and composition B cell pool unperturbed hematopoiesis. Lineage tracing stratified murine based on timing output, revealing a substantial portion originated within restricted neonatal window. In addition B-1a cells, early-life time-stamped included clonally interrelated IgA plasma in gut bone marrow. These were actively maintained by memory...
Abstract Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic cell (HSC) ageing is linked several functional shortcomings. However, besides recent realization that individual HSCs be preset differentially already from young age, also age asynchronously. Evaluating prospects HSC rejuvenation therefore ultimately requires approaching those are functionally affected by...
Abstract Hematopoietic stem cell (HSC) mutations can result in clonal hematopoiesis (CH) with heterogeneous clinical outcomes. Here, we investigate how the state preceding Tet2 mutation impacts pre-malignant phenotype. Using an inducible system for analysis of myeloid progenitors, find that epigenetic features clones at similar differentiation status are highly and functionally respond differently to mutation. Cell stage also influences response indicating origin’s epigenome modulates...
Summary Transitions between subsets of differentiating hematopoietic cells are widely regarded as unidirectional in vivo . Here, we introduce clonal phylogenetic tracer (CP-tracer) that sequentially introduces genetic barcodes, enabling high-resolution analysis ∼100,000 subclones derived from ∼500 individual stem (HSC). This revealed previously uncharacterized HSC functional and identified bidirectional fate transitions myeloid-biased lineage-balanced HSC. Contrary to the prevailing view...
Hematopoietic stem and progenitor cells (HSPCs) in the fetus adult possess distinct molecular landscapes that regulate cell fate change their susceptibility to initiation progression of hematopoietic malignancies. Here, we applied in-depth quantitative proteomics comprehensively describe compare proteome fetal HSPCs. Our data uncover a striking difference complexity cellular proteomes, with more diverse adult-specific HSPC proteomic signatures. The differential protein content HSPCs indicate...
MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of these patients, congenital is very rare transformation usually occurring postnatally. The influence signals on leukemogenesis, such as those mediated by fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that...
Temporally restricted expression of Lin28b promotes generation self-reactive B-1 cells early in life.
The fetal-to-adult switch in hematopoietic stem cell (HSC) behavior is characterized by alterations lineage output and entry into deep quiescence. Here we identify the emergence of megakaryocyte (Mk)-biased HSCs as an event coinciding with this developmental switch. Single-cell chromatin accessibility analysis reveals a ubiquitous acquisition Mk priming signatures during transition. These molecular changes functionally coincide increased amplitude early differentiation events after acute...
Summary Given that FLT 3 expression is highly restricted on lymphoid progenitors, it possible the established role of in regulation B and T lymphopoiesis reflects its high lymphoid‐primed multipotent progenitors ( LMPP s) or common CLP s). We generated a Flt3 conditional knock‐out fl/fl ) mouse model to address direct lymphoid‐restricted subsequent turning Rag1 expression, as well potentially ontogeny‐specific roles lymphopoiesis. Our studies establish prominent 3, independently s s, fetal...
Solid tumors, including gliomas, still represent a challenge to clinicians and first line treatments often fail, calling for new paradigms in cancer therapy. Novel strategies overcome tumor resistance are mainly represented by multi-targeted approaches, cell vector-based therapy is one of the most promising treatment modalities under development. Here, we show that mouse bone marrow-derived mesenchymal stromal cells (MSCs), when primed with low-dose irradiation (irMSCs), undergo changes...
Regulation of granulocyte and macrophage formation was studied by a modified CFU‐C assay. Mouse bone marrow cells were cultured in methylcellulose vitro. After colony counting on d 7, the washed out to determine total cell number per plate, distribution granulocytes macrophages smears. By this procedure it possible study pathway‐specific regulators. The stimulating factor medium conditioned mouse L‐cells appeared specific for line; 99% macrophages. Medium 24 h mononuclear from human blood,...
Cellular barcoding enables the dissection of clonal dynamics in heterogeneous cell populations through single lineage tracing. The labeling hematopoietic stem and progenitor cells (HSPCs) with unique heritable DNA barcodes, makes it possible to resolve donor heterogeneity terms differentiation potential bias at level, subsequent transplantation high-throughput sequencing. Furthermore, cellular allows for bona fide (HSCs) be defined based on functional rather than immunophenotypic parameters....
Single-cell sequencing has enabled the mapping of heterogeneous cell populations in stroma hematopoietic organs. These methodologies provide a lens through which to study previously unresolved heterogeneity at steady state, as well changes type representation induced by extrinsic stresses or during aging. Here, we present step-wise protocols for isolation high-quality stromal from murine and human thymus, bone marrow. Cells isolated these are suitable generating single-cell multiomics...
<h3>Background</h3> B-cells are abundant tumor-infiltrating lymphocytes (TILs) in various solid tumors and exhibit both pro- anti-tumor roles. Regulatory secrete immunosuppressive cytokines the tumor microenvironment (TME), counteracting T-cell responses. Conversely, can produce antibodies, present tumor-specific antigens, inflammatory molecules, form tertiary lymphoid structures (TLSs), Germinal Centre (GC)-like crucial for Antigen-specific significantly influence cancer prognosis;...
Abstract Hematopoietic stem cell mutations can result in clonal hematopoiesis (CH) but the clinical outcomes are heterogeneous. The nature of founder mutation and secondary likely drive emergent neoplastic disease. We investigated how state origin where Tet2 occurs affects susceptibility to that commonly occurring CH mutation. Here, we provide evidence risk is written epigenome origin. By characterizing states underlie myeloid differentiation linking this information an inducible system...