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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2311-2316.
Prepublished online as a Blood First Edition Paper on November 15, 2005; DOI 10.1182/blood-2005-07-2970.
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Submitted July 25, 2005
Accepted October 30, 2005
The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets
Hans B Sieburg, Rebecca H Cho, Bradford Dykstra, Naoyuki Uchida, Connie J Eaves, and Christa E Muller-Sieburg*
Sidney Kimmer Cancer Center, San Diego, CA, USA
Terry Fox Laboratory, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada
* Corresponding author; email: cmuller{at}skcc.org.
Hematopoietic stem cells (HSC) display extensive heterogeneity in their behavior even when isolated as phenotypically homogeneous populations. It is not clear, whether this heterogeneity reflects inherently diverse subsets of HSC or a homogeneous population of HSC diversified by their response to different external stimuli. To address this, we analyzed 97 individual HSC in long-term transplantation assays. HSC clones were obtained from unseparated bone marrow (BM) through limiting dilution approaches. Following transplantation into individual hosts, donor type cells in blood were measured bimonthly and the resulting repopulation kinetics were grouped according to overall shape. Only 16 types of repopulation kinetics were found amongst the HSC clones even though combinatorically 54 groups were possible. All HSC clones, regardless of their origin, could be assigned to this subset of groups and the probability of finding new patterns is negligible. Thus, the full repertoire of repopulating HSC was covered. These data indicate that the HSC compartment consists of a limited number of distinct HSC subsets, each with predictable behavior. Enrichment of HSC (Lin-Rho-SP) changes the representation of HSC types by selecting for distinct subsets of HSC. These data from the steady-state HSC repertoire could provide a basis for the diagnosis of perturbed patterns of HSC potentially caused by disease or aging.
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