Fig. 1

Milestones and technical roadmap of skin organoid generation. a Since the establishment of the first skin organoid by Rheinwald and Green in 1975, significant progress has been made in generating skin organoids, marking various milestones in this field. b The conventional protocol for generating skin organoids involves utilizing the self-organization ability of different cell populations. These cells can be sourced from healthy skin tissue, tissues with inherited diseases, or tumors. Additionally, human pluripotent stem cells (hPSCs) have emerged as another cell source following the development of differentiation protocols. Vascularization is also considered by incorporating human umbilical vein endothelial cells (HUVECs). c However, the generation of skin-specific cells from hPSCs remains a challenge. In 2011, Christiano's group successfully addressed the issue of deriving keratinocytes from hPSCs. d Culturing somatic stem cells is another promising approach. Fuchs et al. separated Blimp1⁺ cells from skin tissue and successfully constructed sebaceous gland organoids through a 12 d 3D culture in vitro. e In 2020, Lee et al. published their work on generating skin organoids entirely from induced pluripotent stem cells (iPSCs). These cyst-like structures are well-stratified and contain rich appendages. iPSC induced pluripotent stem cell, hESC human embryonic stem cell, hPSC human pluripotent stem cell, EDA ectodysplasin A, RA retinoic acid, BMP4 bone morphogenic protein 4, KRT keratin, TP63 tumor protein p63, E8 essential 8 medium, Blimp1 B lymphocyte induced maturation protein 1, bFGF basic fibroblast growth factor, E6SFB E6 medium + SB431542 + bFGF + BMP4, E6LF E6 medium + LDN + bFGF, OMM organoid mature medium