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在 3D 高分辨率 iPSC 衍生棕色前体细胞中敲除增强分化、氧化代谢和棕色化过程。

Knocking Down in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process.

机构信息

Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France.

Faculté de Médecine, CNRS, INSERM, iBV, Université Côte d'Azur, CEDEX 2, F-06107 Nice, France.

出版信息

Cells. 2023 Mar 10;12(6):870. doi: 10.3390/cells12060870.

DOI:10.3390/cells12060870
PMID:36980212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10047013/
Abstract

Human induced pluripotent stem cells (hiPSCs) have the potential to be differentiated into any cell type, making them a relevant tool for therapeutic purposes such as cell-based therapies. In particular, they show great promise for obesity treatment as they represent an unlimited source of brown/beige adipose progenitors (hiPSC-BAPs). However, the low brown/beige adipocyte differentiation potential in 2D cultures represents a strong limitation for clinical use. In adipose tissue, besides its cell cycle regulator functions, the cyclin-dependent kinase inhibitor 2A () locus modulates the commitment of stem cells to the brown-like type fate, mature adipocyte energy metabolism and the browning of adipose tissue. Here, using a new method of hiPSC-BAPs 3D culture, via the formation of an organoid-like structure, we silenced expression during hiPSC-BAP adipogenic differentiation and observed that knocking down potentiates adipogenesis, oxidative metabolism and the browning process, resulting in brown-like adipocytes by promoting UCP1 expression and beiging markers. Our results suggest that modulating levels could be relevant for hiPSC-BAPs cell-based therapies.

摘要

人类诱导多能干细胞（hiPSCs）具有分化为任何细胞类型的潜力，使其成为治疗目的的相关工具，例如基于细胞的治疗。特别是，它们在肥胖治疗方面显示出巨大的潜力，因为它们代表了棕色/米色脂肪祖细胞（hiPSC-BAPs）的无限来源。然而，2D 培养物中低的棕色/米色脂肪细胞分化潜力代表了临床应用的一个强烈限制。在脂肪组织中，除了其细胞周期调节剂功能外，周期蛋白依赖性激酶抑制剂 2A（）基因座调节干细胞向棕色样命运、成熟脂肪细胞能量代谢和脂肪组织褐变的定向分化。在这里，我们使用一种新的 hiPSC-BAPs 3D 培养方法，通过形成类器官样结构，在 hiPSC-BAP 成脂分化过程中沉默 表达，并观察到敲低 可增强脂肪生成、氧化代谢和褐变过程，通过促进 UCP1 表达和 beige 标志物来产生棕色样脂肪细胞。我们的结果表明，调节 水平可能与基于 hiPSC-BAPs 的细胞治疗相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74bd/10047013/fbcf1e975063/cells-12-00870-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74bd/10047013/b994a19654c7/cells-12-00870-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74bd/10047013/fbcf1e975063/cells-12-00870-g011.jpg

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