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Clonal dynamics of native haematopoiesis (Nature 2014)
 Do SC mechanisms govern native non transplant haematopoiesis? Stress
during engraftment and distorted cytokine environment makes it
questionable to what extent their functional characteristics are shared
with cells driving more physiological non-transplant haematopoiesis
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 HSCs were thought to be the only BM cell population capable of longterm self-renewal and multi-lineage differentiation
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(Large
numbers of long lived progenitors rather than SCs)
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 In mice carrying the alleles for the transposase enzyme, transposon
mobilization occurs (into completely distinct insertion sites)
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 A DsRed reporter marks transposon mobilization
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 The tags were analysed in granulocytes, B and T cells from peripheral
blood samples
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 Extremely polyclonal nature of steady-state granulopoiesis
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Granulocytes show myeloid restriction
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The clonal dynamics of post-transplant and steady-state haematopoiesis is
different
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 This suggests that granulocyte production in situ for at least a year is not
predominantly driven by BM cells with the capacity to engraft, but
instead by progenitors with limited transplantation capacity
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 In this model, a large number of progenitors are specified by early
postnatal life, after which there is limited contribution to this pool by LTHSCs
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 It will be important to determine the exact developmental and cellular
origins of the observed long-lived progenitor clones
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It is currently thought that HSCs, given
their known lifelong persistence, are ideal candidates as the target cells
for oncogenic transformation
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 The transposon tagging methods could similarly be used to evaluate
clonal dynamics and evolution in primary tumours and allowing clonal
fate tracking of defined cell populations

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