Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing.
Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing.
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DOI：
10.1016/j.stem.2021.04.003
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发表时间：
2021-07-01
期刊：
影响因子：
23.9
通讯作者：
Shalom-Feuerstein R
中科院分区：
文献类型：
--
作者：
Altshuler A;Amitai-Lange A;Tarazi N;Dey S;Strinkovsky L;Hadad-Porat S;Bhattacharya S;Nasser W;Imeri J;Ben-David G;Abboud-Jarrous G;Tiosano B;Berkowitz E;Karin N;Savir Y;Shalom-Feuerstein R
角膜的可及性和透明性允许强大的干细胞标记和体内细胞命运定位。角膜缘上皮干细胞（LSCs）更新角膜，传统上被认为是罕见的，缓慢循环的细胞，遵循确定性规则决定其自我更新或分化。在这里，我们将单细胞RNA测序和先进的定量谱系追踪相结合，对小鼠边缘上皮进行了深入分析。这些分析揭示了两个LSC种群共存，这些种群分布在独立且定义明确的子区室中，称为“外部”和“内部”边缘。静止外部LSCs的原始群体参与伤口愈合和边界形成，并受作为生态位的T细胞调节。相反，内角膜边缘有活性的LSCs，维持角膜上皮的稳态。定量分析表明，LSC种群数量丰富，遵循随机规律和中性漂移动力学。总之，这些结果表明，离散的LSC群体介导角膜稳态和再生。单细胞rna测序结合定量谱系追踪揭示了两个不同的小鼠LSC群体的存在，特征和动态，它们居住在空间上定义的子区室，称为“外”和“内”边缘。每个LSC种群表现出不同的循环特性、生态位调控和动态平衡与再生功能。
The accessibility and transparency of the cornea permit robust stem cell labeling and in vivo cell fate mapping. Limbal epithelial stem cells (LSCs) that renew the cornea are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. Here, we combined single-cell RNA sequencing and advanced quantitative lineage tracing for in-depth analysis of the murine limbal epithelium. These analysis revealed co-existence of two LSC populations localized in separate and well-defined sub-compartments, coined the “outer” and the “inner” limbus. The primitive population of quiescent outer LSCs participates in wound healing and boundary formation, and are regulated by T cells which serve as a niche. In contrast, the inner peri-corneal limbus hosts active LSCs that maintain corneal epithelial homeostasis. Quantitative analyses suggest that LSC populations are abundant, following stochastic rules and neutral drift dynamics. Together these results demonstrate that discrete LSC populations mediate corneal homeostasis and regeneration. Single cell RNA-sequencing combined with quantitative lineage tracing revealed the existence, signature and dynamics of two distinct murine LSC populations, which reside in spatially defined sub-compartments, termed the “outer” and “inner” limbus. Each LSC populations exhibit distinct cycling properties, regulation by the niche and function under homeostasis and regeneration.
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DOI：
10.3791/53370
发表时间：
2015-12-18
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Amitai-Lange A;Berkowitz E;Altshuler A;Dbayat N;Nasser W;Suss-Toby E;Tiosano B;Shalom-Feuerstein R
通讯作者：
Shalom-Feuerstein R
DOI：
10.1242/dev.197590
发表时间：
2020-12-16
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Ishii R;Yanagisawa H;Sada A
通讯作者：
Sada A
影响因子：
7.5
作者：
Colom, Bartomeu;Jones, Philip H.
通讯作者：
Jones, Philip H.
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：
5.2
作者：
Di Girolamo, N.;Bobba, S.;Lyons, J. G.
通讯作者：
Lyons, J. G.