Clonal analysis of LIMB, DIA and EOM SCs. SCs were isolated from adult Nestin-GFP
mice as described in Figs. 1B and S3A. (A–D) Clonal
cultures were fixed on day 10 and stained with DAPI for quantifying clone size
according to the number of nuclei. (A and B) Examples of (A) low-magnification
whole clone images (DAPI stained), and (B) high-magnification phase images
demonstrating the typical morphology and cell density of average size LIMB, DIA
and EOM clones. (C) Distribution of LIMB, DIA and EOM clones according to the
number of nuclei per clone. Clones are clustered in bins in ascending order
according to the number of nuclei per clone (x-axis) vs. the
percentage of clones in each bin out of total clones analyzed (histograms, left
y-axis). In the cumulative curves, each data point
(round-shaped, right y-axis) shows the percentage of clones out
of total clones analyzed that contain less than, or equal to (≤) the
corresponding number of nuclei per clone size range indicated on the
x-axis bins. (D) Clonal data analyzed in (C) are also
illustrated as boxplots, depicting the quartile distribution, mean (black
crosses) and outliers (red circles, right y-axis) for the
number of nuclei per clone; whisker ranges and outliers were calculated as
previously detailed by us in (Shefer et al.,
2013). Asterisk denotes statistically significant difference in clone
size between EOM vs. LIMB and DIA clones (p<0.01). (E)
Representative phase and fluorescence images of day 21 clones established from
LIMB, DIA and EOM SCs showing Nestin-GFP+ renewal cells with
a typical higher manifestation in EOM clones. (F) Quantification of SC clones
that harbor Nestin-GFP+ cells demonstrates that renewal cells
are consistently more frequent in EOM clones. The relative clone size was also
estimated by categorizing each clone as small, medium, large or X-large
depending on whether the clone occupied a 20×, 10 ×, 4 ×
or several 4 × objective fields, respectively. On day 7, only EOM
cultures displayed clones in the “Large” category. Then, by day
21, solely EOM harbored “X-Large” clones, while clones falling
in the two smaller categories represented only 30% of total clones for
EOM vs. 60% for LIMB cultures. Scale bars, 1 mm (A), 250 μm (B),
50 μm (E).