将小鼠多能干细胞体外分化为产生皮质类固醇的肾上腺皮质细胞。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI:10.1016/j.stemcr.2024.07.010
Ioannis Oikonomakos, Melina Tedesco, Fariba Jian Motamedi, Mirko Peitzsch, Serge Nef, Stefan R Bornstein, Andreas Schedl, Charlotte Steenblock, Yasmine Neirijnck
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引用次数: 0

摘要

将多能干细胞定向分化为特化细胞类型,是广泛应用的宝贵工具。在这里,我们利用单细胞转录组数据,开发了一个将小鼠胚胎干细胞逐步分化为肾上腺皮质细胞的体外分化系统。我们发现,在发育过程中,肾上腺原基被嵌入含有腱鞘蛋白和纤维连接蛋白的细胞外基质中。在分化过程中,将细胞培养在纤维连接蛋白上可增加类固醇生成标记 NR5A1 的表达。此外,在蛋白激酶A(PKA)通路激活剂存在下进行三维培养,可形成由表达肾上腺祖细胞或类固醇生成标记(包括肾上腺皮质特异性酶CYP21A1)的不同类型细胞组成的聚集体。重要的是,体外分化细胞对促肾上腺皮质激素(ACTH)和血管紧张素II做出反应,分别产生糖皮质激素和矿质皮质激素,从而证实了向肾上腺系分化的特异性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vitro differentiation of mouse pluripotent stem cells into corticosteroid-producing adrenocortical cells.

Directed differentiation of pluripotent stem cells into specialized cell types represents an invaluable tool for a wide range of applications. Here, we have exploited single-cell transcriptomic data to develop a stepwise in vitro differentiation system from mouse embryonic stem cells into adrenocortical cells. We show that during development, the adrenal primordium is embedded in an extracellular matrix containing tenascin and fibronectin. Culturing cells on fibronectin during differentiation increased the expression of the steroidogenic marker NR5A1. Furthermore, 3D cultures in the presence of protein kinase A (PKA)-pathway activators led to the formation of aggregates composed of different cell types expressing adrenal progenitor or steroidogenic markers, including the adrenocortical-specific enzyme CYP21A1. Importantly, in-vitro-differentiated cells responded to adrenocorticotropic hormone (ACTH) and angiotensin II with the production of glucocorticoids and mineralocorticoids, respectively, thus confirming the specificity of differentiation toward the adrenal lineage.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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