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胚胎角膜形成过程中鼠眼眶间充质转录组特征的变化。

Transformation of the Transcriptomic Profile of Mouse Periocular Mesenchyme During Formation of the Embryonic Cornea.

机构信息

BioSciences Department, Rice University, Houston, Texas, United States.

出版信息

Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):661-676. doi: 10.1167/iovs.18-26018.

Abstract

PURPOSE

Defects in neural crest development are a major contributing factor in corneal dysgenesis, but little is known about the genetic landscape during corneal development. The purpose of this study was to provide a detailed transcriptome profile and evaluate changes in gene expression during mouse corneal development.

METHODS

RNA sequencing was used to uncover the transcriptomic profile of periocular mesenchyme (pNC) isolated at embryonic day (E) 10.5 and corneas isolated at E14.5 and E16.5. The spatiotemporal expression of several differentially expressed genes was validated by in situ hybridization.

RESULTS

Analysis of the whole-transcriptome profile between pNC and embryonic corneas identified 3815 unique differentially expressed genes. Pathway analysis revealed an enrichment of differentially expressed genes involved in signal transduction (retinoic acid, transforming growth factor-β, and Wnt pathways) and transcriptional regulation.

CONCLUSIONS

Our analyses, for the first time, identify a large number of differentially expressed genes during progressive stages of mouse corneal development. Our data provide a comprehensive transcriptomic profile of the developing cornea. Combined, these data serve as a valuable resource for the identification of novel regulatory networks crucial for the advancement of studies in congenital defects, stem cell therapy, bioengineering, and adult corneal diseases.

摘要

目的

神经嵴发育缺陷是角膜先天发育不良的一个主要致病因素,但人们对角膜发育过程中的遗传景观知之甚少。本研究的目的是提供详细的转录组图谱,并评估小鼠角膜发育过程中基因表达的变化。

方法

采用 RNA 测序技术,揭示了胚胎第 10.5 天眼眶间充质(pNC)和第 14.5 天、第 16.5 天胚胎角膜的转录组图谱。通过原位杂交验证了几个差异表达基因的时空表达情况。

结果

pNC 和胚胎角膜之间的全转录组分析鉴定了 3815 个独特的差异表达基因。通路分析显示,差异表达基因富集于信号转导(视黄酸、转化生长因子-β 和 Wnt 通路)和转录调控。

结论

我们的分析首次在小鼠角膜发育的渐进阶段鉴定出大量差异表达基因。我们的数据提供了发育中角膜的全面转录组图谱。这些数据结合在一起,为鉴定新的调控网络提供了有价值的资源,这些网络对先天性缺陷、干细胞治疗、生物工程和成人角膜疾病的研究进展至关重要。

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