Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells.

Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells.
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DOI:
10.1038/s41596-022-00681-y
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发表时间:
2022-05
期刊:
影响因子:
14.8
通讯作者:
Koehler, Karl R.
Koehler, Karl R.
中科院分区:
生物学1区
文献类型:
--
作者:
Lee, Jiyoon;van der Valk, Wouter H.;Serdy, Sara A.;Deakin, CiCi;Kim, Jin;Le, Anh Phuong;Koehler, Karl R.

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人体皮肤使用分布在体表上的数百万根毛发和腺体来充当外部屏障、温度调节器和刺激传感器。大规模生产具有这些附属物的人体皮肤将是有益的,但具有挑战性。在这里,我们描述了在三维体外培养系统中完全从同质的人类多能干细胞群体中产生毛发皮肤组织的详细方案。在确定的培养条件下,在2周的时间内诱导多能干细胞分化为表面外胚层和颅神经嵴细胞,这两种细胞分别在每个类器官单位中产生表皮和真皮。经过60天的孵化,皮肤类器官产生毛囊。到第130天,皮肤类器官达到完全复杂,包括分层皮肤层、色素毛囊、皮脂腺、默克尔细胞和感觉神经元,重现了妊娠第18周胎儿皮肤组织的细胞组成和结构。使用该方案,皮肤类器官可在培养物中维持长达150天,使类器官可用于研究基本皮肤生物学、模型疾病,并进一步用于皮肤组织的重建或再生。
Human skin uses millions of hairs and glands distributed across the body surface to function as an external barrier, thermoregulator, and stimuli sensor. The large-scale generation of human skin with these appendages would be beneficial, but is challenging. Here, we describe a detailed protocol for generating hair-bearing skin tissue entirely from a homogeneous population of human pluripotent stem cells in a three-dimensional in vitro culture system. Defined culture conditions are used over a 2-week period to induce differentiation of pluripotent stem cells to surface ectoderm and cranial neural crest cells, which give rise to the epidermis and dermis, respectively, in each organoid unit. After 60 days of incubation, the skin organoids produce hair follicles. By day ~130, the skin organoids reach full complexity and contain stratified skin layers, pigmented hair follicles, sebaceous glands, Merkel cells, and sensory neurons, recapitulating the cell composition and architecture of fetal skin tissue at week-18 of gestation. Skin organoids can be maintained in culture using this protocol for up to 150 days, enabling the organoids to be used to investigate basic skin biology, model disease, and further, the reconstruction or regeneration of skin tissue.
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影响因子: 11.8
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