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University of Cambridge > Department of Oncology > Computational Biology Group > Research

Somatic Cell Mitotic Clocks

There is interest in the problem of inferring human stem cell dynamics from genomic variations, but while there are several methods for marking and following stem cell fates, such experimental approaches do not work well in humans


Outline

Schematic of bisulfite-clone-and-sequence strategy

In collaboration with the Shibata laboratory (USC), we proposed a novel approach to this problem that involves the comparison of methylation patterns sampled from somatic cells and used this method to infer the typical number of stem cells in a colon crypt. The method is however more general and has been applied to many different tissues.

In addition to investigating the continuous genealogy with clonal evolution of stem cells typified by colon crypt niches, we have examined human hair follicles, an example of a punctuated genealogy caused by clonal succession. We have also reconstructed continuous genealogies for small intestinal crypts, endometrial glands and T cells, punctuated genealogies for neutrophils and B cells, and static genealogies for tissue showing no increase in mitotic age with chronological aging, such as brain and heart.

Selected publications of ours in this area
  • Nicolas P, Kim K-M, Shibata D, and Tavare S The stem cell population of the human colon crypt: analysis via methylation patterns. PLoS Comput Biol 2007 3, e28
  • Shibata D, and Tavare S. Counting divisions in a human somatic cell tree: how, what and why? Cell Cycle 2006 5, 610–614
  • Kim JY, Tavare S, and Shibata D Human hair genealogies and stem cell latency BMC Biol 2006 4, 2.