Unique activities of two overlapping PAX6 retinal enhancers.
Unique activities of two overlapping PAX6 retinal enhancers.
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两个重叠的PAX6视网膜增强剂的独特活动。
DOI：
10.26508/lsa.202302126
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发表时间：
2023-11
影响因子：
4.4
通讯作者：
Bhatia, Shipra
中科院分区：
文献类型：
--
作者：
Uttley, Kirsty;Papanastasiou, Andrew S.;Lahne, Manuela;Brisbane, Jennifer M.;Macdonald, Ryan B.;Bickmore, Wendy A.;Bhatia, Shipra
斑马鱼高分辨率成像和单细胞RNA测序的独特组合揭示了发育眼睛增强剂的细胞类型特异性活性。增强子通过精确调节空间、时间和细胞类型特异性基因表达在发育中发挥关键作用。增强子中的序列变体与疾病有关;然而，由于缺乏对增强子通常具有活性的精确细胞类型和发育阶段的了解，因此确定这些变体的功能后果具有挑战性。PAX 6是眼睛发育的主要调节因子，具有包含驱动眼睛中表达的多个增强子的调节景观。这些增强子是否具有相加、冗余或不同的功能尚不清楚。在这里，我们描述了精确的细胞类型和两个PAX 6视网膜增强剂，HS 5和NRE的调节活性。在双增强子-报告基因斑马鱼胚胎中使用活成像和单细胞RNA测序的独特组合，我们揭示了这些增强子的时空活性差异。我们的研究结果表明，虽然重叠，这些增强子在不同的细胞类型有不同的活动，因此可能是非冗余的功能。这项工作表明，独特的细胞类型特异性活动，可以发现明显相似的增强剂时，在高分辨率的体内研究。
A unique combination of high-resolution imaging and single-cell RNA sequencing in zebrafish reveals cell type-specific activities of developmental eye enhancers. Enhancers play a critical role in development by precisely modulating spatial, temporal, and cell type-specific gene expression. Sequence variants in enhancers have been implicated in diseases; however, establishing the functional consequences of these variants is challenging because of a lack of understanding of precise cell types and developmental stages where the enhancers are normally active. PAX6 is the master regulator of eye development, with a regulatory landscape containing multiple enhancers driving the expression in the eye. Whether these enhancers perform additive, redundant or distinct functions is unknown. Here, we describe the precise cell types and regulatory activity of two PAX6 retinal enhancers, HS5 and NRE. Using a unique combination of live imaging and single-cell RNA sequencing in dual enhancer–reporter zebrafish embryos, we uncover differences in the spatiotemporal activity of these enhancers. Our results show that although overlapping, these enhancers have distinct activities in different cell types and therefore likely nonredundant functions. This work demonstrates that unique cell type-specific activities can be uncovered for apparently similar enhancers when investigated at high resolution in vivo.
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影响因子：
5.5
作者：
Angueyra JM;Kindt KS
通讯作者：
Kindt KS
影响因子：
2.6
作者：
Griffin, C;Kleinjan, DA;van Heyningen, V
通讯作者：
van Heyningen, V
影响因子：
46.9
作者：
Dann, Emma;Henderson, Neil C.;Marioni, John C.
通讯作者：
Marioni, John C.
影响因子：
4.5
作者：
Dey, Kushal K.;Hsiao, Chiaowen Joyce;Stephens, Matthew
通讯作者：
Stephens, Matthew
DOI：
10.1111/ejn.14257
发表时间：
2018-12
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Rulands S;Iglesias-Gonzalez AB;Boije H
通讯作者：
Boije H