Hair-bearing human skin generated entirely from pluripotent stem cells.
Hair-bearing human skin generated entirely from pluripotent stem cells.
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DOI：
10.1038/s41586-020-2352-3
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发表时间：
2020-06
期刊：
影响因子：
64.8
通讯作者：
Koehler KR
中科院分区：
文献类型：
--
作者：
Lee J;Rabbani CC;Gao H;Steinhart MR;Woodruff BM;Pflum ZE;Kim A;Heller S;Liu Y;Shipchandler TZ;Koehler KR
皮肤是一个多层器官，配有附属物(即毛囊和腺体)，对调节体液滞留和温度、抵御外部压力以及调节触觉和痛感至关重要。在培养物和生物工程移植物中重建附属物皮肤仍然是一个尚未满足的生物医学挑战。在这里，我们报告了一种由人类多能干细胞产生复杂皮肤的器官培养系统。我们利用转化生长因子β和成纤维细胞生长因子信号通路的分步调节，共同诱导球形细胞内的颅骨上皮细胞和神经脊细胞。在4-5个月的孵化过程中，我们观察到囊状皮肤器官的出现，它由复层的表皮、富含脂肪的真皮和带有皮脂腺的色素毛囊组成。感觉神经元和雪旺细胞组成的网络形成了神经束，这些神经束以器官状毛囊中的默克尔细胞为靶细胞，模仿人类的触摸回路。单细胞RNA测序和与胎儿样本的直接比较表明，皮肤有机物质相当于发育中期的人类面部皮肤。此外，我们还发现，当移植到裸鼠身上时，皮肤有机化合物形成了平坦的毛发皮肤。综上所述，我们的结果表明，几乎完全的皮肤可以在体外自组装，并用于体内重建皮肤。我们预计，皮肤类器官将成为未来人类皮肤发育、疾病模型或重建外科研究的基础。
The skin is a multi-layered organ equipped with appendages (i.e. follicles and glands) critical for regulating bodily fluid retention and temperature, guarding against external stresses, and mediating touch and pain sensation. Reconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge. Here, we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use step-wise modulation of the TGFβ and FGF signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During 4–5 months incubation, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis, and pigmented hair follicles equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking human touch circuitry. Single-cell RNA-sequencing and direct comparison to foetal specimens suggest that skin organoids are equivalent to human facial skin in the second-trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted on nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate skin organoids will be foundational to future studies of human skin development, disease modelling, or reconstructive surgery.
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通过下一代技术，可以洞悉干细胞生态裂的复杂性。
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