Zhu Xuming, Xu Mingang, Portal Celine, Lin Yvonne, Ferdinand Alyssa, Peng Tien, Morrisey Edward E, Dlugosz Andrzej A, Castellano Joseph M, Lee Vivian, Seykora John T, Iomini Carlo, Millar Sarah E
Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
bioRxiv. 2024 Aug 10:2024.08.09.607015. doi: 10.1101/2024.08.09.607015.
Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identified markers for stem cell populations that maintain distinct regions of the gland and uncovered Hh signaling as a key regulator of stem cell proliferation. Consistent with this, human Meibomian gland carcinoma exhibited increased Hh signaling. Aged glands displayed decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.
睑板腺分泌富含脂质的睑脂，可防止泪液蒸发。与衰老相关的睑板腺萎缩可能部分是由于干细胞耗竭所致，并且与蒸发型干眼病相关，这是一种缺乏有效治疗方法的常见病症。睑板腺干细胞的身份、生态位以及控制其活性的信号目前尚不清楚。通过使用单细胞核RNA测序（snRNA-seq）、体内谱系追踪、体外实时成像以及小鼠遗传学研究，我们确定了维持睑板腺不同区域的干细胞群体标志物，并发现Hh信号是干细胞增殖的关键调节因子。与此一致的是，人类睑板腺癌显示出Hh信号增加。衰老的睑板腺显示Hh和表皮生长因子（EGF）信号减少、神经支配不足以及生态位成纤维细胞中I型胶原蛋白缺失，这表明腺上皮细胞及其周围微环境的改变均导致了与年龄相关的睑板腺退变。这些发现为治疗与衰老相关的睑板腺萎缩提供了新方法。
