Deciphering the spatio-temporal transcriptional and chromatin accessibility of human retinal organoid development at the single cell level
Deciphering the spatio-temporal transcriptional and chromatin accessibility of human retinal organoid development at the single cell level
复制标题
在单细胞水平上破译人类视网膜类器官发育的时空转录和染色质可及性
DOI：
10.1101/2023.07.19.549507
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Dorgau B
中科院分区：
文献类型：
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作者：
Dorgau B
由于获得早期人眼样本的限制，人类视网膜发育早期阶段的分子信息仍然很少。多能干细胞衍生的视网膜类器官（RO）为研究早期视网膜发生提供了前所未有的机会。使用单细胞RNA-seq和空间转录组学的组合，我们首次提出了RO发育的单细胞时空转录组。我们的数据表明，RO重演视网膜发生的关键事件，包括视泡/杯形成，存在一个假定的睫状缘区，视网膜祖细胞的出现和它们有序分化为视网膜神经元。结合scRNA-与scATAC-seq数据，我们能够揭示在类器官发育的每个阶段可接近的染色质上的细胞类型特异性转录因子结合基序，并表明染色质可接近性与发育中的人类视网膜高度相关，但在一些视网膜神经元的时间出现和丰度方面存在一些差异。
Molecular information on the early stages of human retinal development remains scarce due to limitations in obtaining early human eye samples. Pluripotent stem cell-derived retinal organoids (ROs) provide an unprecedented opportunity for studying early retinogenesis. Using a combination of single cell RNA-seq and spatial transcriptomics we present for the first-time a single cell spatiotemporal transcriptome of RO development. Our data demonstrate that ROs recapitulate key events of retinogenesis including optic vesicle/cup formation, presence of a putative ciliary margin zone, emergence of retinal progenitor cells and their orderly differentiation to retinal neurons. Combining the scRNA- with scATAC-seq data, we were able to reveal cell-type specific transcription factor binding motifs on accessible chromatin at each stage of organoid development, and to show that chromatin accessibility is highly correlated to the developing human retina, but with some differences in the temporal emergence and abundance of some of the retinal neurons.