Barcoding in situ to study steady state hematopoiesis

by Alexey Bersenev on October 7, 2014 · 0 comments

in hematopoietic, methods

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Few days ago, Harvard’s investigator Fernando Camargo published results of long-term study, which challenges our current understanding of steady state hematopoiesis. Remarkably, the authors showed that long-lasting polyclonal progenitors contribute to normal blood turnover the most rather than hematopoeitic stem cells. It’s actually not a big news if you follow discussions from recent studies of steady state hematopoiesis. However, what makes Camargo’s study special is a methodology.

The authors used very sophisticated and quite complicated approach to label blood cells with genetic tags (barcodes). Remarkably, this kind of labeling was done in situ – no cell isolation, viral transduction and transplantation! The labeling can be induced by a drug and barcodes could be tracked in any time points during chase period (after drug withdrawal) in different cell populations of blood and bone marrow. From press release:

A transposon is a piece of genetic code that can jump to a random point in DNA when exposed to an enzyme called transposase. Camargo’s approach works using transgenic mice that possess a single fish-derived transposon in all of their blood cells. When one of these mice is exposed to transposase, each of its blood cells’ transposons changes location. The location in the DNA where a transposon moves acts as an individual cell’s barcode, so that if the mouse’s blood is taken a few months later, any cells with the same transposon location can be linked back to its parent cell.

This is probably the best system ever described to study steady state hematopoiesis. Theoretically it allows to “track clonal fate of any cell population”. Imagine that you can precisely watch clonal cell behavior in dynamics during regeneration, disease, carcinogenesis, development and aging. It reminds me lineage tracing with higher resolution. Well, at this point we don’t know it it’s going to work for other tissues. Despite its great potential, the technique is quite complicated and required “special engineered mice strains”. In 2012 interview, Camargo said that “it was hard to make transgenic mice and it took 7 years”.

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