Clonal Haematopoiesis in Ischemic Stroke
Description: Stroke incidence is rising with aging, as does the prevalence of leukaemia-associated mutations in
hematopoietic stem cells, known as clonal haematopoiesis (CH). In an incident stroke cohort, we identified a
strong association of TET2 mutations and clone size with combined vascular endpoints in a three-year follow-
up. The impact of CH on stroke damage and outcome is unknown. We will model CH in mice using TET2 KO
or WT BM chimeras and various clone sizes. Stroke will be induced by transient middle cerebral artery
occlusion and invading BM cells that have a myeloid bias due to the TET2 mutation will be traced by CD45.1
or YFP expression. Damage and structural plasticity will be assessed by MRI (T2 incidence maps and
diffusion tensor imaging) and functional recovery by daily behavioral testing. The fate, and activity of invading
mutant cells in ischemic brains will be determined by index sorting of YFP/CD45.1 and scRNAseq using
MARS-seq 2.0 and histology. The recipient response will be studied by RiboTag-based translatome analysis.
Cytokine profiles of TET2 KO and WT will be analysed in vitro by proteomics, followed by confirmatory
microdialysis after stroke. Mutant cells contributing to the pool of perivascular macrophages of pial vessels
will be analysed by 3D-mapping of Lyve1+ TET2 KO or WT BM transplants. Our team has the skills to
analyze the complex pathophysiology, the fate of invading myeloid cells, and their impact on the
microenvironment and outcome following stroke.
Funder: Narodowe Centrum Badań i Rozwoju
Amount: PLN 909,900
Funding type: research
Funder scheme: Projekty ENIAC JU, ARTEMIS, ECSEL, Projekty w ramach partnerstw publiczno-publicznych: EDCTP2, EMPIR, EUROSTARS 2, AAL, ERA-NET, ERA-NET Plus, ERA-NET Cofund, JPI
Start date: 2024-07-01
End date: 2026-06-30
Investigator: Anna Malik
Institution: Uniwersytet Warszawski
Funded outputs count: 2
Funder award ID: NeuronC2/II/34/CH/Stroke/2023
OpenAlex ID: G7598045840