miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids,STEM CELLS

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miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids
STEM CELLS ( IF 4.0 ) Pub Date : 2020-09-01 , DOI: 10.1002/stem.3272
Lucie Peskova ₁ , Denisa Jurcikova ₁ , Tereza Vanova _{1,

2} , Jan Krivanek ₁ , Michaela Capandova ₁ , Zuzana Sramkova ₃ , Jana Sebestikova _{1,

4} , Magdalena Kolouskova ₁ , Hana Kotasova _{1,

2} , Libor Streit ₅ , Tomas Barta ₁

Affiliation

MicroRNAs (miRNAs), a class of small, noncoding RNA molecules, represent important regulators of gene expression. Recent reports have implicated their role in the cell specification process acting as “fine‐tuners” to ensure the precise gene expression at the specific stage of cell differentiation. Here, we used retinal organoids differentiated from human pluripotent stem cells (hPSCs) as a model to closely investigate the role of a sensory organ‐specific and evolutionary conserved miR‐183/96/182 cluster. Using a miRNA tough decoy approach, we inhibited the miR‐183/96/182 cluster in hPSCs. Inhibition of the miRNA cluster resulted in an increased expansion of neuroepithelium leading to abnormal “bulged” neural retina in organoids, associated with upregulation of neural‐specific and retinal‐specific genes. Importantly, we identified PAX6, a well‐known essential gene in neuroectoderm specification, as a target of the miR‐183/96/182 cluster members. Taken together, the miR‐183/96/182 cluster not only represents an important regulator of PAX6 expression, but it also plays a crucial role in retinal tissue morphogenesis.

中文翻译：

miR-183/96/182簇是分化人视网膜类器官中靶向PAX6表达的重要形态发生因子

MicroRNA (miRNA) 是一类小的非编码 RNA 分子，代表基因表达的重要调节因子。最近的报告表明它们在细胞特化过程中充当“微调器”，以确保细胞分化特定阶段的精确基因表达。在这里，我们使用从人类多能干细胞（hPSC）分化的视网膜类器官作为模型来仔细研究感觉器官特异性和进化保守的 miR-183/96/182 簇的作用。使用 miRNA 强诱饵方法，我们抑制了 hPSC 中的 miR-183/96/182 簇。抑制 miRNA 簇会导致神经上皮细胞扩张增加，从而导致类器官中神经视网膜异常“凸出”，这与神经特异性和视网膜特异性基因的上调有关。重要的是，我们确定了 PAX6（神经外胚层规范中众所周知的必需基因）作为 miR-183/96/182 簇成员的靶标。综上所述，miR-183/96/182簇不仅是PAX6表达的重要调节因子，而且在视网膜组织形态发生中也发挥着至关重要的作用。

更新日期：2020-09-01

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