Estimating cell lineage from distributions of randomly introduced markers

Cell lineage of a multicellular organism has been analysed by introducing a genetic or chemical marker that is inherited from a cell to its daughter c ells and is detectable even after several cell divisions. To construct a co mplete cell lineage, all the cells at different developmental stages need t o be identified, and then the intracellular marker must be introduced to ea ch cell. In this paper, I study a new method of estimating cell lineage bas ed on distributions of intercellular markers observed at a single stage, wh ich are introduced randomly at earlier stages. Assumptions are: (1) cell li neage is invariant between embryos; (2) a small number of cells are marked in each experiment; and (3) the total number of replicate experiments is su fficiently large. Then we identify the most likely cell lineage pattern (or tree topology) as the one that requires the least marker insertions to be compatible with the observed distributions of cell markers. This method is essentially the same as the principle of persimony widely used for ancestra l phylogeny reconstruction in evolutionary biology. When the total number o f cells is small, we can generate all the possible cell lineages and calcul ate the minimum number of marker insertions for each candidate, and then ch oose the cell lineage that requires the least marker insertions. If the num ber of cells is large, we can use clustering method in which a pair of cell s with the highest correlation in marker labelling are merged sequentially. The efficiency of the clustering method in estimating the correct cell lin eage is confirmed by computer simulations. Finally, the clustering method i s applied to reconstruct the cell lineage of ascidian from experimental dat a. (C) 1999 Academic Press.