小柯机器人

荷兰大学医学中心Hans Clevers和Marie Bannier-Hélaouët共同合作，近期取得重要工作进展。他们利用人类结膜类器官研究眼表面稳态和疾病。相关研究成果2024年1月11日在线发表于《细胞—干细胞》杂志上。

据介绍，覆盖眼睛的结膜上皮包含两种主要细胞类型：产生粘液的杯状细胞和分泌水的角质形成细胞，角质形成细胞在其顶面上呈现粘蛋白。

研究人员描述了代表小鼠和人类结膜的长期扩展的类器官和气液界面。原代和培养的人结膜的单细胞RNA表达图谱显示角质形成细胞表达多种抗菌肽并鉴定结膜簇细胞。IL-4/-13暴露增加杯状和簇状细胞分化，并显著改变结膜分泌组。人NGFR+基底细胞被鉴定为双能结膜干细胞。结膜培养物可被单纯疱疹病毒1型（HSV1）、人类腺病毒8型（hAdV8）和严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）感染。添加阿昔洛韦可逆转HSV1感染，而缺乏批准药物治疗的hAdV8感染可被西多福韦抑制。研究人员记录了由HSV1和hAdV8诱导的转录程序。最后，研究人员证明结膜类器官可以移植。

总之，人类结膜类器官培养物共同使结膜（病理）生理学的研究成为可能。

附：英文原文

Title: Human conjunctiva organoids to study ocular surface homeostasis and disease

Author: Marie Bannier-Hélaout, Jeroen Korving, Ziliang Ma, Harry Begthel, Amir Giladi, Mart M. Lamers, Willine J. van de Wetering, Nobuyo Yawata, Makoto Yawata, Vanessa L.S. LaPointe, Mor M. Dickman, Rachel Kalmann, Saskia M. Imhoff, Johan H. van Es, Carmen López-Iglesias, Peter J. Peters, Bart L. Haagmans, Wei Wu, Hans Clevers

Issue&Volume: 2024-01-11

Abstract: The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13 exposure increases goblet and tuft cell differentiation and drastically modifies the conjunctiva secretome. Human NGFR+ basal cells are identified as bipotent conjunctiva stem cells. Conjunctival cultures can be infected by herpes simplex virus 1 (HSV1), human adenovirus 8 (hAdV8), and SARS-CoV-2. HSV1 infection was reversed by acyclovir addition, whereas hAdV8 infection, which lacks an approved drug therapy, was inhibited by cidofovir. We document transcriptional programs induced by HSV1 and hAdV8. Finally, conjunctival organoids can be transplanted. Together, human conjunctiva organoid cultures enable the study of conjunctival (patho)-physiology.

DOI: 10.1016/j.stem.2023.12.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00438-1

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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