One can align clonal transplantation outcomes along a predictable output of different cell types, if one considers that different HSC clones will start this cycle of mature blood cell production at different time points post-transplantation 6/9
This is why we devised a new set of kinetic-based parameters which capture the dynamic changes in mature cell output and provide a mathematical framework against which to unlock the underlying biology HSC heterogeneity 8/9
Finally, the myeloid-biased clone generated a platelet-biased outcome early on after transplantation, and had the greatest remaining reserves of HSPCs in the bone marrow at the end time point 5/9
Following some amazing discussions with colleagues at EHA about our recent publication in
@natcellbio.nature.com, here are some important points showing why considering HSC reconstitution kinetics will make you re-think the concept of lineage biases rdcu.be/fkASJ 1/9
Mick Milsom
Mick Milsom
Mick Milsom
Zooming into the lymphoid biased clone, which has no HSPC reserves in the bone marrow at the end point, we can see that at earlier time points, it would have been classified as balanced or even myeloid biased 3/9
Although I've cherry-picked four examples of single HSC transplantation outcomes that clearly illustrate the point I wanted to make, in the manuscript we've used the new kinetics parameters to statistically validate these concepts using >1,000 single cell transplantation outcomes
Mick Milsom
This explains why a multipotent clone can be considered to have a specific lineage-bias purely dependent on the arbitrary time point at which the analysis was performed (arrows). So how can we meaningfully assess HSC potencies and function? 7/9
Coming next (when I have a few spare minutes), I’ll explain why different HSC kinetics relates to lineage output (spoiler: it relates to competition between slow and fast clones), but if you can’t wait, feel free to check out the manuscript rdcu.be/fkASJ 9/9
Looking at the outcomes of 4 single HSC transplants, we can see that at the 24 week end point analysis of peripheral blood, one clone (top row) would be classically characterized as lymphoid biased; two as balanced; and one as myeloid-biased 2/9
Likewise, the two balanced clones, which do have some HSPC reserves in the BM at the end point, also demonstrated a different lineage outcome at earlier time points, having cycled through a myleoid-biased output 4/9
