Somatostatin signalling promotes the differentiation of rod photoreceptors in human pluripotent stem cell-derived retinal organoid.
Somatostatin signalling promotes the differentiation of rod photoreceptors in human pluripotent stem cell-derived retinal organoid.
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生长抑素信号传导促进人多能干细胞衍生的视网膜类器官中视杆光感受器的分化。
DOI：
10.1111/cpr.13254
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发表时间：
2022-07
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
--
作者：
干细胞衍生的感光细胞替代疗法是治疗视网膜变性疾病的一种有前途的策略。3D视网膜类器官的发展已经允许产生光感受器。然而，由于感光细胞命运决定的分子机制知识不足，没有策略来富集特定的感光细胞亚型。因此，我们的目的是探索生长抑素信号转导在人多能干细胞源性感光细胞分化中的未表征功能。从人胚胎干细胞获得3D视网膜类器官。已发表的人类视网膜发育的单细胞RNA测序数据集被用于进一步研究感光细胞分化的转录调控。采用免疫荧光染色、慢病毒转染、真实的实时定量聚合酶链反应（PCR）和蛋白质印迹法（Western blotting）等方法进行检测。我们发现生长抑素受体2（SSTR 2）介导的信号传导对于前体阶段的视杆细胞分化至关重要。在人3D视网膜类器官中加入同源配体生长抑素促进了视杆细胞的分化，抑制了视锥细胞的产生。此外，我们发现，杆光感受器的发生调制的内源性生长抑素特异性分泌的发展视网膜神经节细胞。我们的研究确定了SSTR 2信号作为一种新的外源性调节器的感光前体细胞的视杆细胞命运的决定，这扩大了感光细胞发育的功能信号通路的剧目，并揭示了感光细胞富集策略的优化。生长抑素受体2（SSTR 2）介导的信号传导调节hESC衍生的视网膜类器官中感光细胞前体的命运决定。SSTR2信号的激活对于视杆细胞的分化是至关重要的。具体而言，生长抑素增加视杆细胞的生产，而SSTR 2拮抗剂促进光感受器前体细胞对视锥细胞的命运偏好。
Stem cell‐derived photoreceptor replacement therapy is a promising strategy for the treatment of retinal degenerative disease. The development of 3D retinal organoids has permitted the production of photoreceptors. However, there is no strategy to enrich a specific photoreceptor subtype due to inadequate knowledge of the molecular mechanism underlying the photoreceptor fate determination. Hence, our aim is to explore the uncharacterized function of somatostatin signalling in human pluripotent stem cell‐derived photoreceptor differentiation. 3D retinal organoids were achieved from human embryonic stem cell. The published single‐cell RNA‐sequencing datasets of human retinal development were utilized to further investigate the transcriptional regulation of photoreceptor differentiation. The assays of immunofluorescence staining, lentivirus transfection, real‐time quantitative polymerase chain reaction and western blotting were performed. We identified that the somatostatin receptor 2 (SSTR2)‐mediated signalling was essential for rod photoreceptor differentiation at the precursor stage. The addition of the cognate ligand somatostatin in human 3D retinal organoids promoted rod photoreceptor differentiation and inhibited cone photoreceptor production. Furthermore, we found that the genesis of rod photoreceptors was modulated by endogenous somatostatin specifically secreted by developing retinal ganglion cells. Our study identified SSTR2 signalling as a novel extrinsic regulator for rod photoreceptor fate determination in photoreceptor precursors, which expands the repertoire of functional signalling pathways in photoreceptor development and sheds light on the optimization of the photoreceptor enrichment strategy. The somatostatin receptor 2 (SSTR2)‐mediated signalling modulates the fate determination of photoreceptor precursors in hESC‐derived retinal organoids. The activation of SSTR2 signalling is critical for rod photoreceptor differentiation. Specifically, somatostatin increases rod photoreceptor production, while SSTR2 antagonist promotes the fate bias of photoreceptor precursors towards the cone photoreceptors.
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影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
影响因子：
4.8
作者：
Khanna, Hemant;Akimoto, Masayuki;Swaroop, Anand
通讯作者：
Swaroop, Anand
影响因子：
2.9
作者：
Kanamori, A;Nakamura, M;Negi, A
通讯作者：
Negi, A
影响因子：
3.1
作者：
Lukomska, Agnieszka;Dobrzanski, Grzegorz;Kossut, Malgorzata
通讯作者：
Kossut, Malgorzata
维生素的机制是哺乳动物和苍蝇视觉系统中的代谢和缺乏。
影响因子：
2.7
作者：
Dewett D;Lam-Kamath K;Poupault C;Khurana H;Rister J
通讯作者：
Rister J