fate, with NR cells choosing between symmetric
duplication, asymmetric division, and symmetric
differentiation with probabilities independent of
the cell generation (Fig. 2H and fig. S3).
Thus, on the basis of these observations, we
considered the quantitative fate behavior of R cells.
Given the sequential pattern of symmetric and
asymmetric divisions, we questioned whether
R cells might be following a developmental-like
program, switching irreversibly from a phase of
proliferative (symmetrical) divisions to a phase
of neurogenic (asymmetrical) divisions, as ob-
served during cortical development (Fig. 4A,
fig. S6A, and table S2) (30). Using a statistical
modeling approach, we quantitatively assessed
the viability of this hypothesis by fitting the
lengths of putative proliferative and neurogenic
phases against average clonal properties (methods).
This simple developmental-like paradigm yielded
predictions of the proliferative output, the cell
fate distributions, and the average clonal com-
position over time that were in agreement with
the observed data within the theoretically pre-
dicted variability (Fig. 4, B to D, and methods).
As a consistency check, we also assessed whether
the observed sequential fate pattern could rep-
resent the chance outcome of stochastic fate be-
havior, with R cells becoming progressively
biased away from self-renewal toward differ-
entiation over time (figs. S6 and S7). However,
660 9 FEBRUARY 2018 • VOL 359 ISSUE 6376 sciencemag.org SCIENCE
Fig. 2. The mode of NSPC division is
associated with individual cell division
history. (A) Self-renewal duration (time
between first and last division in each
lineage) of R cells (9.6 ± 1.3 days; n =
39). (B) Distribution of the final number
of cells per active clone (n = 42
lineages). Open circles represent individual clones. (C) Chronic in vivo imaging before and after cell division
illustrates asymmetric cell division of
R cells. A large overlap is evident in the
cellular morphology before (red arrowhead and red outline) and after (green
arrowhead and green outline) R cell
division. The black arrowhead points at
the asymmetrically generated daughter
cell. (D) A morphometric index (including
circularity and process length; details
are given in the methods) shows little
deviation in cell morphology before and
after cell division (9.6 ± 1.8%; n = 9).
(E) Heat map representing the frequencies
of modes of division of R cells (all divisions and division rounds 1 to 3; n = 68
divisions total). The division mode
changes from predominantly asymmetric
(division 1) to a more symmetric differentiating division (divisions 2 and 3).
N, neuron; A, astrocyte. (F) Example of
an asymmetric division of an R cell
(lineage 40; fig. S3). (G) Example of a
symmetric division of an R cell (lineage
13). Mother cells are indicated with arrowheads and daughter cells with arrows.
(H) Heat map representing the frequencies
of cell division modes of NR cells (all
divisions and division rounds 1, 3, and 5; n =
153 divisions). (I) Example of a symmetric
NR cell division (lineage 1). (J) Example
of an asymmetric NR cell division (lineage
3). The NR daughter continues to divide.
Mother and daughter cells are indicated as
in (F) and (G). (K) Cell division time (TD)
of R and NR cells for different divisions.
(L) The times until next cell division of
sister cells originating from a single R
mother cell are correlated (Pearson’s r =
0.77; *P < 0.00001; n = 22 pairs). (M) The
TD of sister cells originating from a single
NR mother are not correlated (Pearson’s
r = 0.44; P = 0.08; n = 16 pairs). Each
plus sign represents a pair of sister cells.
Red lines, means; error bars, SEM. Scale
bars, 20 mm [(C), (F), (G), (I), and (J)].