Fig. 1: Apoptotic corpses are transiently cleared by neighbouring HFSCs in late catagen.
From: Stem cells tightly regulate dead cell clearance to maintain tissue fitness
a, Schematic of the hair cycle depicting inactive or old HFSC niche (grey) and active or current niche in uORS. Middle ORS (mORS) and lORS die in catagen. Ana, anagen; Cat, catagen; Telo, telogen. b, Left, ultrastructure of engulfed corpses (white arrowheads) within catagen uORS. Outlined regions are magnified and pseudocoloured on the right. White arrows denote apoptotic cells and dashed lines denote dermo-epithelial border. Graphs show quantification of phagocytic cells, ratio of phagocytic to apoptotic cells per hair follicle (HF) (n = 25 hair follicles, 4 mice per stage (AnaVI; Telo); or n = 38 hair follicles (CatII), 51 hair follicles (CatIV–VI), 45 hair follicles (CatVII–VIII), 6 mice per stage) and number of corpses per phagocytic cell (n = 7 hair follicles). Bu, bulge; DP, dermal papilla. Scale bars, 2 μm. c, Left, single-cell RNA sequencing (scRNA-seq) strategy for hair follicle epithelial cells. Right, uniform manifold approximation and projection (UMAP) representation and clustering of transcriptomes across the hair cycle. HG, hair germ. d, UMAP representations coloured by aggregate gene-set score with catagen cluster outlined. e, Schematic depicting apoptotic cell recognition by neighbouring phagocyte. PS, phosphatidylserine. f, Expression of TAM-family phagocytic receptors (left) and lysosomal genes (right) in Sox9-creER+;R26-Brainbow2.1 fluorophore HFSCs that are double-fluor-positive (double+) or single-fluor-positive (single+) per mouse. n = 3 (Telo), n = 4 (AnaVI, CatII), or n = 6 (CatIV–VI, CatVII–VIII) mice per stage. g, Quantification of unengulfed corpses (left) and phagocytic HFSCs (right) from wild-type (WT) versus Mertk-knockout (KO) mice. n = 20 WT, n = 26 Mertk-KO (CatIV–VI) and n = 53 WT, n = 28 Mertk-KO (CatVII–VII) hair follicles quantified, 3 mice per stage. h, Strategy (left) using recombinant annexin V (AnxV) to block corpse-exposed phosphatidylserine during catagen (contralateral vehicle (Veh) injections). Quantifications of unengulfed corpses (middle) and phagocytic HFSCs (right). Ten hair follicles per mouse, n = 3 mice per condition. 1d, 1 day. Pairwise independent two-sided Student’s t-tests, P values indicated. NS, not significant (P > 0.05). In box plots, the centre line is the median, box edges delineate first and third quartiles and whiskers extend to 1.5× the inter-quartile range. Further details on statistics and reproducibility in Methods. See Extended Data Figs. 1–3 for additional supporting experiments and Supplementary Table 1 for differential gene expression analysis.
