Resolving the number of HSCs and their progeny that actively contribute
to hematopoiesis and tracking the contribution of individual HSCs
to each of the different blood cell lineages to determine is important
to answer the cellular basis for decreased efficiency in tissue
homeostasis and thus tissue function in the elderly.
Our hypothesis is that aging reduces clonality, decreases cell turnover
and shifts lineage determination of HSCs in part through altered
Cdc42 signaling. So our main foucus is to Quantify changes in clonality,
lineage determination and HSC turnover upon aging.we will use the
barcoding technology to determine the contribution of clonally marked
HSCs and their progeny to hematopoiesis upon aging. We are also
interested to dissect the contribution of HSC intrinsic versus extrinsic
effects as well as the role of Cdc42 activity in altering cellular
turnover, clonality and lineage determination upon HSC aging.