SSBD:repository

Tissue stem cells (SCs) are generated from an embryonic progenitor population through organ-specific morphogenetic events. Although tissue SCs are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly owing to the lack of specific markers that exclusively label prospective SCs. Here, by combining marker-independent long-term three-dimensional (3D) live imaging and single-cell transcriptomics, we captured cellular dynamics, dynamic cell lineages, and transcriptome changes in the entire epidermis of developing mouse hair follicles (HFs). We found that different epidermal lineage precursors were aligned in a two-dimensional (2D) concentric manner in the basal layer of the hair placode. Each concentric ring zone acquired unique transcriptomes and telescoped out to form longitudinally aligned 3D cylindrical compartments. Prospective bulge SCs were derived from the peripheral ring zone of the placode, irrespective of cell division orientation, but not from previously suggested suprabasal cells. We also identified 13 gene clusters in which their ensemble expression dynamics drew the entire transcriptional landscape of epidermal lineage diversification, coinciding with cell lineage data. Combining these findings with insect appendage development, we provide a generalized model termed the “telescope model” wherein 2D concentric zones in the placode telescope out to form 3D longitudinally aligned cylindrical compartments.