EpiHTStem · Understanding the Maintenance and Heritability of Hematopoietic Stem Cell Memories: High-Throughput Drug Screening Meets Single-Cell Barcoding
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-04-01 → 2025-03-31
- EU contribution
- €165,313
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Understanding the Maintenance and Heritability of Hematopoietic Stem Cell Memories: High-Throughput Drug Screening Meets Single-Cell Barcoding
Hematopoietic stem cells (HSCs), are a group of cells living in the bone marrow that have the capacity to generate all of the immune cells present in our blood. As we age, HSCs are exposed to different changes in their environment (like infections) that have the capacity to alter their function. Particularly, as we age, HSCs start to lose the capacity to generate blood. These alterations in the capacity to generate blood of HSCs have been associated with increased chances of developing leukemias and to cardiovascular diseases and, until now, there are not treatments to improve and rejuvenate the activity of HSCs. Our objective with this project is to create a novel scientific platform that could allow us to screen for compounds (hundreds of them at the same time) that could "heal" this HSCs and give them again the capacity to produce blood, in the same way that they could do when they were younger, for example.
Data: CORDIS, © European Union
Project objective
During the development of multicellular organisms, cells from the same niche can be stochastically exposed to different signals and stimuli, and this variability has the potential to create epigenetic heterogeneity across cell populations. Importantly, this heterogeneity can confer individual cells different functional properties or different capacities to respond to the same stimuli. During the last decade, multiple laboratories have reported the existence of hematopoietic stem cell (HSC) clones with different functional behaviors that are transmitted to daughter cells. Very interestingly, these behaviors are transmitted to their progeny even after transplantation, suggesting that heritable epigenetic components are required to establish and maintain them. In this regard, some questions arise: Which epigenetic regulators are involved in the maintenance of these memories? Which regions associate with specific HSC fate memories? And, how heritable are different chromatin states in dividing HSCs? Until recently, we were very limited by the current technologies to answer these questions. Now, recent advances in single-cell lineage tracing, single-cell multiomics and ex-vivo HSC expansion cultures can be leveraged to provide a robust mechanistic understanding of clonal heritability of HSC fates and states. Consequently, this proposal aims to combine new lineage tracing techniques, multimodal single-cell sequencing and functional assays to: (1) create an atlas of clonally-heritable epigenetic states associated to specific functional HSC behaviors and (2) to identify epigenetic regulators that are required to maintain and transmit HSC memories associated with specific HSC fates.
Original text from CORDIS.
Participants
- FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) · BarcelonaCoordinatorSpain
Links
- View on CORDIS
- DOI: 10.3030/101109276
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e50d1c3e48&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e51a8af00e&appId=PPGMS
Data: CORDIS, © European Union