entity called a cell lineage tree. The root of the tree represents the fertilized egg, the leaves of the tree represent the person's extant cells, and branches in the tree capture every single cell division in the person's history. Science knows precisely the cell lineage tree of only one organism a worm called Caenorhabditis elegans that reaches its full size of 1 millimeter and 1,000 cells in 36 hours. By comparison, a newborn mouse, weighing only a few grams, has about 1 billion cells. An average person has about 100 trillion cells. Understanding the structure and dynamics of the human cell lineage tree in development, growth, renewal, aging, and disease is a central and urgent quest of biology and medicine. The challenge of uncovering the Human Cell Lineage Tree is reminiscent, both in nature and in scope, to the challenge faced by the Human Genome Project at its inception and, in fact, its results will decisively contribute to the functional translation and ultimate understanding of the genome sequence. A technological leap of a magnitude similar to the one that occurred during the Human Genome Project is required for the success of the human cell lineage project, and the biological and biomedical impact of such a success could be of a magnitude similar, if not larger than that of the Human Genome Project. Central open problems in biology and medicine are in effect questions about the human cell lineage tree: its structure and its dynamics in development, growth, renewal, aging, and disease. Consequently, knowing the Human Cell Lineage Tree would resolve these problems and entail a leapfrog advance in human knowledge and health. Many central questions in biology and medicine that are actually specific questions about the Human cell lineage tree, in health and disease: Which cancer cells initiate relapse after chemotherapy? Which cancer cells can metastasize? Do insulin-producing beta cells renew in healthy adults? Do eggs renew in adult females? Which cells renew in healthy and in unhealthy adult brain? Knowing the human cell lineage tree would answer all these questions and more. Fortunately, our cell lineage tree is implicitly encoded in our cells’ genomes via mutations that accumulate when body cells divide. Theoretically, it could be reconstructed with high precision by sequencing every cell in our body, at a prohibitive cost. Practically, analyzing only highly-mutable fragments of the genome is sufficient for cell lineage reconstruction. Shapiro's lab has developed