Keratin-14-Positive Precursor Cells Spawn a Population of Migratory Corneal Epithelia that Maintain Tissue Mass throughout Life.
Keratin-14-Positive Precursor Cells Spawn a Population of Migratory Corneal Epithelia that Maintain Tissue Mass throughout Life.
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DOI：
10.1016/j.stemcr.2017.08.015
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发表时间：
2017-10-10
影响因子：
5.9
通讯作者：
Di Girolamo N
中科院分区：
文献类型：
--
作者：
Richardson A;Lobo EP;Delic NC;Myerscough MR;Lyons JG;Wakefield D;Di Girolamo N
对于促进角膜形成和维持的上皮干细胞(SCs)的动态了解甚少。在这里，我们使用K14CreERT2-五彩纸屑(五彩纸屑)小鼠、复杂的成像和计算建模来追踪这些细胞在胚胎发育和成年生活中的起源和命运。我们发现，角蛋白-14(K14+)表达的前体细胞被定义并广泛分布于E16.5角膜，之后它们在眼皮张开之前经历了增殖和扩散的循环。K14+克隆性斑块从中央角膜消失，取而代之的是角膜缘来源的K14+条纹，这一发现与溴脱氧尿苷标记保留研究一致。我们还阐明了SC克隆在生命过程中丢失的机制，并提出这是由于种群不对称和中性漂移造成的。最后，我们确定赤道移行中线的发生是由于狭窄的鼻颞区细胞凋亡的结果，也就是眨眼时眼皮相遇的地方。胚胎K14+祖细胞来源的克隆性扩张是双相性的角膜缘，而不是中央性，上皮干细胞补充角膜上皮，年龄相关的LESC动态符合群体非对称性中性漂移正常克隆迁移模式被中央角膜细胞凋亡改变Richardson等人。说明胚胎发育后期角膜上皮细胞发育的双相性。中央角膜的祖细胞在出生后丢失，取而代之的是外围角膜缘的祖细胞，其年龄相关的动态与种群的不对称性一致。中央角膜上皮细胞的凋亡改变了正常的克隆性迁移模式。
The dynamics of epithelial stem cells (SCs) that contribute to the formation and maintenance of the cornea are poorly understood. Here, we used K14CreERT2-Confetti (Confetti) mice, sophisticated imaging, and computational modeling to trace the origins and fate of these cells during embryogenesis and adult life. We show that keratin-14 (K14+)-expressing progenitors are defined and widely distributed across the E16.5 cornea, after which they undergo cycles of proliferation and dispersal prior to eyelid opening. K14+ clonal patches disappear from the central cornea and are replaced by limbal-derived K14+ streaks, a finding that aligned with bromodeoxyuridine label-retaining studies. We also elucidated the mechanism by which SC clones are lost during life and propose this is due to population asymmetry and neutral drift. Finally, we established that the occurrence of an equatorial migratory mid-line is a consequence of apoptosis in a narrow nasal-temporal region, the site where eyelids meet during blinking. Embryonic K14+-progenitor-derived clonal expansion is biphasic Limbal, not central, epithelial stem cells replenish the corneal epithelium Age-related LESC dynamics are consistent with population asymmetric neutral drift Normal clonal migration patterns are altered by central corneal apoptosis Richardson et al. demonstrate the biphasic nature of corneal epithelial development during late embryogenesis. Progenitor cells of the central cornea are lost during post-natal life, replaced by those in the peripheral limbus, whose age-related dynamics align with population asymmetry. Apoptosis within the central corneal epithelium alters normal clonal migration patterns.
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影响因子：
16.6
作者：
Lobo EP;Delic NC;Richardson A;Raviraj V;Halliday GM;Di Girolamo N;Myerscough MR;Lyons JG
通讯作者：
Lyons JG
影响因子：
--
作者：
Mort RL;Ramaesh T;Kleinjan DA;Morley SD;West JD
通讯作者：
West JD
影响因子：
4.6
作者：
Li J;Xiao Y;Coursey TG;Chen X;Deng R;Lu F;Pflugfelder SC;Li DQ
通讯作者：
Li DQ
影响因子：
1.2
作者：
Dorà NJ;Hill RE;Collinson JM;West JD
通讯作者：
West JD
影响因子：
4.4
作者：
Nagasaki, T;Zhao, J
通讯作者：
Zhao, J