The Annals of Applied Statistics

Bayesian inference and model choice in a hidden stochastic two-compartment model of hematopoietic stem cell fate decisions

Youyi Fong, Peter Guttorp, and Janis Abkowitz

Full-text: Open access


Despite rapid advances in experimental cell biology, the in vivo behavior of hematopoietic stem cells (HSC) cannot be directly observed and measured. Previously we modeled feline hematopoiesis using a two-compartment hidden Markov process that had birth and emigration events in the first compartment. Here we perform Bayesian statistical inference on models which contain two additional events in the first compartment in order to determine if HSC fate decisions are linked to cell division or occur independently. Pareto Optimal Model Assessment approach is used to cross check the estimates from Bayesian inference. Our results show that HSC must divide symmetrically (i.e., produce two HSC daughter cells) in order to maintain hematopoiesis. We then demonstrate that the augmented model that adds asymmetric division events provides a better fit to the competitive transplantation data, and we thus provide evidence that HSC fate determination in vivo occurs both in association with cell division and at a separate point in time. Last we show that assuming each cat has a unique set of parameters leads to either a significant decrease or a nonsignificant increase in model fit, suggesting that the kinetic parameters for HSC are not unique attributes of individual animals, but shared within a species.

Article information

Ann. Appl. Stat., Volume 3, Number 4 (2009), 1695-1709.

First available in Project Euclid: 1 March 2010

Permanent link to this document

Digital Object Identifier

Mathematical Reviews number (MathSciNet)

Zentralblatt MATH identifier

Stochastic two-compartment model hidden Markov models reversible jump MCMC hematopoiesis stem cell asymmetric division


Fong, Youyi; Guttorp, Peter; Abkowitz, Janis. Bayesian inference and model choice in a hidden stochastic two-compartment model of hematopoietic stem cell fate decisions. Ann. Appl. Stat. 3 (2009), no. 4, 1695--1709. doi:10.1214/09-AOAS269.

Export citation


  • Abkowitz, J., Catlin, S. and Guttorp, P. (1996). Evidence that hematopoiesis may be a stochastic process in vivo. Nature Medicine 2 190–197.
  • Abkowitz, J., Catlin, S., McCallie, M. and Guttorp, P. (2002). Evidence that the number of hematopoietic stem cells per animal is conserved in mammals. Blood 100 2665–2667.
  • Abkowitz, J., Golinelli, D., Harrison, D. and Guttorp, P. (2000). In vivo kinetics of murine hemopoietic stem cells. Blood 96 3399–3405.
  • Abkowitz, J., Linenberger, M., Newton, M., Shelton, G., Ott, R. and Guttorp, P. (1990). Evidence for the maintenance of hematopoiesis in a large animal by the sequential activation of stem-cell clones. Proc. Natl. Acad. Sci. USA 87 9062–9066.
  • Abkowitz, J., Linenberger, M., Persik, M., Newton, M. and Guttorp, P. (1993). Behavior of feline hematopoietic stem cells years after busulfan exposure. Blood 82 2096–2103.
  • Abkowitz, J., Ott, R., Holly, R. and Adamson, J. (1988). Clonal evolution following chemotherapy-induced stem cell depletion in cats heterozygous for glucose-6-phosphate dehydrogenase. Blood 71 1687–1692.
  • Catlin, S. (1997). Statistical inference for partially observed Markov population processes. Ph.D. dissertation, Univ. Washington.
  • Catlin, S., Abkowitz, J. and Guttorp, P. (2001). Statistical inference in a two-compartment model for hematopoiesis. Biometrics 57 546–553.
  • Catlin, S., Busque, L., Gale, R., Guttorp, P. and Abkowitz, J. (2009). Estimating the replication rate of human hematopoietic stem cells in vivo. Submitted.
  • Chang, J., Palanivel, V., Kinjyo, I., Schambach, F., Intlekofer, A., Banerjee, A., Longworth, S., Vinup, K., Mrass, P., Oliaro, J., Killeen, N., Orange, J., Russell, S., Weninger, W. and Reiner, S. (2007). Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315 1687–1691.
  • Czechowicz, A., Kraft, D., Weissman, I. and Bhattacharya, D. (2007). Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science 318 1296–1299.
  • Golinelli, D. (2000). Bayesian inference in hidden stochastic population processes. Ph.D. dissertation, Univ. Washington.
  • Golinelli, D., Guttorp, P. and Abkowitz, J. (2006). Bayesian inference in a hidden stochastic two-compartment model for feline hematopoiesis. Mathematical Medicine and Biology 23 153–172.
  • Guttorp, P., Newton, M. and Abkowitz, J. (1990). A stochastic model for haematopoiesis in cats. Mathematical Medicine and Biology 7 125–143.
  • Knoblich, J. (2008). Mechanisms of asymmetric stem cell division. Cell 132 583–597.
  • Newton, M., Guttorp, P. and Abkowitz, J. (1992). Bayesian inference by simulation in a stochastic model from hematology. In Proceedings of the 24th Symposium on the Interface: Computing Science and Statistics 449–455. Interface Foundation of North America, Fairfax Station, VA.
  • Raftery, A., Newton, M., Satagopan, J. and Krivitsky, P. (2007). Estimating the integrated likelihood via posterior simulation using the harmonic mean identity. Bayesian Statistics 8 (J. M. Bernardo, M. J. Bayarri and J. O. Berger, eds.) 371–416. Oxford Univ. Press, Oxford.
  • Reynolds, J. and Ford, E. (1999). Multi-criteria assessment of ecological process models. Ecology 80 538–553.
  • Robert, C. and Casella, G. (2004). Monte Carlo Statistical Methods. Springer, New York.
  • Schofield, R. (1978). The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4 7–25.
  • Schroeder, T. (2007). Asymmetric cell division in normal and malignant hematopoietic precursor cells. Cell Stem Cell 1 479–481.
  • Shepherd, B., Guttorp, P., Lansdorp, P. and Abkowitz, J. (2004). Estimating human hematopoietic stem cell kinetics using granulocyte telomere lengths. Exp. Hematol. 32 1040–1050.
  • Shepherd, B., Kiem, H., Lansdorp, P., Dunbar, C., Aubert, G., LaRochelle, A., Seggewiss, R., Guttorp, P. and Abkowitz, J. (2007). Hematopoietic stem-cell behavior in nonhuman primates. Blood 110 1806–1813.
  • Vincent, T. and Grantham, W. (1981). Optimality in parametric systems. Wiley, New York.
  • Wu, M., Kwon, H., Rattis, F., Blum, J., Zhao, C., Ashkenazi, R., Jackson, T., Gaiano, N., Oliver, T. and Reya, T. (2007). Imaging hematopoietic precursor division in real time. Cell Stem Cell 1 541–554.
  • Yamashita, Y. and Fuller, M. (2008). Asymmetric centrosome behavior and the mechanisms of stem cell division. J. Cell Biol. 180 261–266.
  • Yu, B. (1995). Comment: Extracting more diagnostic information from a single run using the cusum path plot. Statist. Sci. 10 54–58.