Abstract
The competitive repopulation assay in recipients has emerged as the gold standard test that enables characterization of hematopoietic stem cells (HSCs) by their capacity for reconstitution of the lymphohematopoietic system. When combined with a limiting dilution design, this assay, termed limiting-dilution competitive repopulation assay (LDCRA) allows measurement of HSC numbers in vivo. Thus far, the statistical single-hit Poisson model (SHPM) has played a prominent role in analyzing LDCRAs to estimate HSC frequencies. This chapter presents a review of a new statistical method for analyzing LDCRAs, called multi-cell Poisson modeling, with aim to more accurately estimate the frequency of HSCs. Multi-cell Poisson models (MCPM) stand for a general family of Poisson models that extend the SHPM hypothesis, including the traditional SHPM as a special case of the model series. Through examples of re-analyses of LDCRAs from previously published papers, it is shown the ability of MCPM to model LDCRAs in comparison to the traditional SHPM. The results emphasize that MCPM can provide more reliable HSC frequency estimates than obtained from the exclusive use of the SHPM. It is concluded that the use of proper Poisson models alternative to the traditional SHPM appears as critical to ensure accurate HSC frequency estimates, and MCPM should be routinely used to model LDCRAs. More generally, MCPM provide substantial refinement in the art of modeling limiting dilution assays.
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Acknowledgment
The authors would like to thank Philippe Carbonnel for expert design of Fig. 2.1.
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Bonnefoix, T., Callanan, M. (2012). Hematopoietic Stem Cell Frequency Estimate: Statistical Approach to Model Limiting Dilution Competitive Repopulation Assays. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 2. Stem Cells and Cancer Stem Cells, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2016-9_2
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