Page 288 - 20dynamics of cancer

STEM CELLS: POPULATION GENETICS 273

linear stem
cell history
in tissue
renewal

stem differentiation
exponential
growth in
development

tissue precursor

division from
zygote to
precursor

zygote

Figure 13.1 Lineage history of cells in renewing tissues. All cells trace their
ancestry back to the zygote. Each tissue, or subset of tissue, derives from a pre-
cursor cell; n p rounds of cell division separate the precursor cell from the zy-
gote. From a precursor cell, n e rounds of cell division lead to exponential clonal
expansion until the descendants differentiate into the tissue-specific stem cells
that seed the developing tissue. In a compartmental tissue, such as the intes-
tine, lineage history of the renewing tissue follows an essentially linear path, in
which each cellular history traces back through the same sequence of stem divi-
sions (Figure 12.2). At any point in time, a cell traces its history back through n s
stem cell divisions to the ancestral stem cell in the tissue, and n = n p + n e + n s
divisions back to the zygote. Modified from Frank and Nowak (2003).

mutation accumulation in cell lineages: the distribution of mutations in
an exponentially expanding clone of cells.
To study the Luria-Delbrück problem, we must distinguish between
mutational events and the number of cells that carry a mutation. Fig-
ure 13.2 shows an example in which one cell divides through three
3
cellular generations to yield N = 2 = 8 descendants. This exponen-
tial growth requires a total of N − 1 = 7 cell divisions. Each cell di-
vision causes one cell to branch into two descendants, so there are
2(N − 1) = 14 branches in which DNA is copied and a mutational event