Objective Haematopoietic stem cells (HSC) reside in the bone marrow, from where they maintain immune cells, erythrocytes and platelets. To function correctly, they depend on their localisation within highly specialised niches, where cell-cell and -matrix interactions as well as medium- and long-range molecular signals are integrated to instruct them to either remain quiescent, or to generate progeny that will maintain both the stem cell pool and the differentiated lineages. Studies based on HSC transplantation assays have identified several signalling pathways and bone marrow cell types as regulators of HSC function; however the full picture of the cellular and molecular components of the HSC niche remains elusive because of lack of direct observation over time. HSC subpopulations have been identified based on their proliferative behaviour and it is likely that either migration between different microenvironments or transient modifications of the niche structure mediate changes in HSC fate in response to perturbations such as infection or leukaemia development.I pioneered the combination of confocal and two-photon microscopy to visualise single HSC and their progeny within the bone marrow of live mice and here I propose to combine advanced microscopy techniques with multi-colour genetic lineage marking and highly sensitive expression profiling to track HSC and their clonal progeny in vivo in real time and to study the cellular and molecular composition of their niches during steady state and when responding to infection and leukaemia development. This work will uncover whether functionally distinct HSC subpopulations reside in anatomically distinct niches or rather all HSC niches are in principle equivalent, but change over time to mediate changes in HSC fate balance. The results obtained will provide a comprehensive picture of HSC niche dynamics, which will be critical for the development of regenerative medicine approaches based on in vivo or ex vivo expansion of HSC. Fields of science natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesbasic medicineimmunologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinetransplantationmedical and health sciencesclinical medicineoncologyleukemia Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE EU contribution € 1 699 724,00 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Brooke Alasya (Ms.) Principal investigator Cristina Lo Celso (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE United Kingdom EU contribution € 1 699 724,00 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Brooke Alasya (Ms.) Principal investigator Cristina Lo Celso (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data