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孕激素受体在诱导多能干细胞(iPSCs)中持续表达。

Progesterone receptor is constitutively expressed in induced Pluripotent Stem Cells (iPSCs).

机构信息

Angelo Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, 25123, Brescia, Italy.

Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, 25123, Brescia, Italy.

出版信息

Stem Cell Rev Rep. 2024 Nov;20(8):2303-2317. doi: 10.1007/s12015-024-10776-6. Epub 2024 Aug 22.

DOI:10.1007/s12015-024-10776-6
PMID:39168923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11554879/
Abstract

Induced Pluripotent Stem Cells (iPSCs) are nowadays a common starting point for wide-ranging applications including 3D disease modeling (i.e. organoids) and in future regenerative medicine. Physiological processes like homeostasis, cell differentiation, development and reproduction are tightly regulated by hormones through binding to their transmembrane or nuclear receptors of target cells. Considering their pleiotropic effect, take into account also their expression in an iPSCs-based disease modeling would better recapitulate the molecular events leading to 3D organoid development and disease study. Here we reported the expression pattern of estrogen receptor (ERα) and progesterone receptor (PR) in four different iPSCs, obtained from CD34 + progenitor cells and skin fibroblasts with four different methods. Expression of ERα and PR mRNA were significantly downregulated in iPSCs as well as fibroblasts compared to MCF7 positive control. Immunofluorescence (IF) staining detected only the expression of PR protein in all the different iPSCs cell lines, while ERα was not detectable. By flow cytometry analysis we observed that the ~ 65% of the total population of iPSCs cells expressed only PR, with 100% fold increase compared to HSPCs and fibroblasts, while ERα was not expressed. Our results collectively demonstrated for the first time that the reprogramming of somatic cells into iPSCs leads to the expression of PR receptor.

摘要

诱导多能干细胞(iPSCs)如今是广泛应用的常见起点,包括 3D 疾病建模(即类器官)和未来的再生医学。生理过程,如内稳态、细胞分化、发育和繁殖,通过与靶细胞的跨膜或核受体结合,由激素紧密调节。考虑到它们的多效性效应,还应考虑到它们在基于 iPSCs 的疾病建模中的表达,这将更好地概括导致 3D 类器官发育和疾病研究的分子事件。在这里,我们报道了四种不同的 iPSCs 中雌激素受体(ERα)和孕激素受体(PR)的表达模式,这些 iPSCs 是从 CD34+祖细胞和皮肤成纤维细胞中通过四种不同的方法获得的。与 MCF7 阳性对照相比,iPSCs 和成纤维细胞中 ERα 和 PR mRNA 的表达均显著下调。免疫荧光(IF)染色仅在所有不同的 iPSCs 细胞系中检测到 PR 蛋白的表达,而 ERα 则不可检测。通过流式细胞术分析,我们观察到 iPSCs 细胞群体中约 65%仅表达 PR,与 HSPCs 和成纤维细胞相比,表达水平增加了 100%,而 ERα 则不表达。我们的研究结果首次表明,体细胞重编程为 iPSCs 会导致 PR 受体的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/8fcb7c8205a5/12015_2024_10776_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/78f9aff7478a/12015_2024_10776_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/4120f624862c/12015_2024_10776_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/de9183e31bda/12015_2024_10776_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/8fcb7c8205a5/12015_2024_10776_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/a9d8d9cccefa/12015_2024_10776_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/59e5e8bf428f/12015_2024_10776_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/eb5725d6327a/12015_2024_10776_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/61a023127048/12015_2024_10776_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/78f9aff7478a/12015_2024_10776_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/4120f624862c/12015_2024_10776_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/de9183e31bda/12015_2024_10776_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d7/11554879/8fcb7c8205a5/12015_2024_10776_Fig8_HTML.jpg

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