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Comment 08

Please cite this contribution as follows: Alexey [Bersenev]. Ilya, I have nothing against your interpretation of these studies. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_08. doi:10.3205/maximowaward_2012_blog-comment_08

This contribution is provided under the following license: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Alexey. May 31, 2012 at 6:35 am

Ilya,

I have nothing against your interpretation of these studies. I agree, everyone can interprets it in different ways. I’m personally with agreement of all conclusions from the studies on HSC heterogeneity done by Eaves and Nakauchi groups.

What do you mean under “clonal analysis”? What assay? Lineage tracing? Colony assay? What classical assay for HSC self-renewal are you talking about? Can your give a reference? Lineage tracing give as mostly information about stem cell fate, division and differentiation history. In transplantation assay your can measure all of these parameters. Serial transplant is not manipulation of group of cells. As I told you, in primary, you transplant a single cell. You can track exactly the same HSC (equal to cell-ancestor) in bone marrow, sort them and transplant again. But we don’t need to do that for following transplants, that’s why we take whole marrow started from 2nd round.

Please give an example, how “clonal analysis” would assess HSC self-renewal better than transplantation assays.

I don’t see where I denied my own opinion. I said if cell passed serial transplant we call it “stem cell”. I understand if someone disagree with this definition. Every assay have limitations.

In terms of heterogeneity definition. There is no such definition set in HSC field. But everybody understand what other people are talking about. In our case heterogeneity refers to functional differences between phenotypically similar types of HSC. For example, Lin-/cKit+/Sca+/CD34-/CD48-/CD150+ HSC could have few different patterns of repopulation, different cell cycle status and kinetics, different gene expression profile. You can figure out the whole heterogeneity things when you start to do single cell assays. Because the whole population (mixed) HSC could behave in the same manner.

You can call HSC as one population, which consist of few functionally different subsets (subpopulations/ clones) or call it as different HSC populations. It doesn’t matter. I’d disagree that HSC transplant assay is highly conditional. if it would be, we will see heterogeneity even in primary transplant of the whole marrow, without HSC purification. We use a special mice – genetically identical, same age, hosted in pathogen-free conditions, undergo exactly the same conditioning and receiving the same post-transplant care – to ensure minimal influence of extrinsic factors. Also, I think, people have done some work which indicate that HSC heterogeneity is intrinsic and not depend completely on extrinsic factors (need to double check this).

This contribution is provided under the following license: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Please cite this contribution as follows: Alexey [Bersenev]. Ilya, I have nothing against your interpretation of these studies. Blog comment, Maximow Award contest, May 2012. Cell Ther Transplant/Maximow Award, May 2012;blog-comment_08. doi:10.3205/maximowaward_2012_blog-comment_08

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