Fig. 3: Pax7-ablation model enables evaluation of human stem cell niche formation in the absence of mouse Pax7 cell competition.
From: Regenerating human skeletal muscle forms an emerging niche in vivo to support PAX7 cells
a, Cartoon depicting hypotheses for SMPC association with human-only myofibres in the Pax7-ablation model (Pax7-ablation (DTX) mdx-NSG). Top: the occupied niche hypothesis predicts SMPCs cannot home to chimeric niches occupied by endogenous satellite cells, and the regenerative niche hypothesis predicts mouse SCs take up position in chimeric niches during regeneration. Bottom: engraftable Pax7 ablation mouse shows expected results for occupied niche and regenerative niche hypotheses. b, Cartoon of ablation mouse model generation and Pax7 cell numbers (white boxes) in Pax7-ablated and non-ablated control mice after 7 days of TMX treatment (resulting in Pax7 ablation or DTX), mean ± standard deviation, N = 5 mice, t-test *P = 0.0003. Tibialis anterior muscles of Pax7-ablated mice are atrophic; some individual myofibres of Pax7-ablated muscle undergo hypertrophy as measured by haematoxylin and eosin staining. c, Human foetal SMPCs increase PAX7+ numbers in Pax7-ablation mice. Representative images show co-staining of human nuclei (red), PAX7 cells (green) and 4′,6-diamidino-2-phenylindole (DAPI). White boxes indicate human PAX7 cells, and yellow boxes indicate mouse Pax7 SCs. Mean ± standard deviation of human PAX7 cells are quantified from Pax7-ablated and non-ablated mice, N = 5 per group, t-test, *P < 0.0004. d, Location of foetal PAX7+ cells are quantified 30 days post engraftment. Scale bar, 50 μm. Inset shows that human PAX7 foetal SMPCs are associated with small human-only myofibres relative to non-ablated controls, N = 5 per group, t-test, *P = 0.034.
