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The model of coexistence 2 populations of adult stem cells

It is becoming more and more clear for researchers who are studying adult stem cells, that the population of these cells in any given tissue is very heterogeneous. Even if the population of adult stem cells express the same surface markers, detectable by flow cytometry, they can have different functional properties, gene expression profile and be in different stages of the cell cycle. It is important to know this kind of heterogeneity in terms of understanding physiological tissue turnover and cancer development.

The recent review by Linheng Li and Hans Clevers [1], published in Science, proposed the model of co-existence of quiescent and active adult stem cells in mammals. I’d like to point out that they didn’t propose it initially – it was done 2-3 years ago by Andreas Trumpp group for hematopoietic stem cells [2] (HSC), but rather extrapolate it to other adult stem cell populations, such as hair and intestinal stem cells. Furthermore, they nicely shaped this model in the concept of stem cell niche and extrinsic signals, regulating cell divisions and fate.

I pooled some data from Andreas Trumpp’s model [3] for HSC, some thoughts from this review, and and from Marieke Essers paper [4] and made a table. This table summarize the main model points for HSC.

characteristics dormant HSC active HSC
primed, self-renewing
phenotype LSK/CD34-/Flk2-/CD48-/CD150+
% in HSC pool ~ 15% ~ 85%
quiescence +++ +
self-renewal rate +++ +
proliferation + +++
replication genes off on
metabolism hibernation/ hypoxia active
function repair in emergency normal blood turnover
niche endosteal vascular
signaling Wnt-off/BMP-on Wnt-on/BMP-off
activation signals active HSC depletion/ Interferon-alpha progenitors depletion
feedback loop +++ +

The new – dormancy model of coexistence of quiescent adult stem cell subpopulations, proposed by Andreas Trumpp group:

dormant(Adapted from Marieke Essers and Andreas Trumpp, 2008-2009)

It is maybe too early to accept this model completely, but it look very nice and logical to me. Nevertheless, some things remain unclear. For example, what can make an active HSC become a dormant HSC during homeostasis? Also, I think it’s premature to divide them by bone marrow niche: dormant in endosteal, active in vascular (central marrow). This review convince me more that there is some kind of universal pattern in organization of adult stem cell populations across different tissues. What do you think?

Also read:
Mapping quiescence of hematopoietic stem cells [2]