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用化学定义条件快速将猪多能干细胞转化为巨噬细胞。

Rapid conversion of porcine pluripotent stem cells into macrophages with chemically defined conditions.

机构信息

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi, China.

College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.

出版信息

J Biol Chem. 2024 Jan;300(1):105556. doi: 10.1016/j.jbc.2023.105556. Epub 2023 Dec 12.

Abstract

A renewable source of porcine macrophages derived from pluripotent stem cells (PSCs) would be a valuable alternative to primary porcine alveolar macrophages (PAMs) in the research of host-pathogen interaction mechanisms. We developed an efficient and rapid protocol, within 11 days, to derive macrophages from porcine PSCs (pPSCs). The pPSC-derived macrophages (pPSCdMs) exhibited molecular and functional characteristics of primary macrophages. The pPSCdMs showed macrophage-specific surface protein expression and macrophage-specific transcription factors, similar to PAMs. The pPSCdMs also exhibited the functional characteristics of macrophages, such as endocytosis, phagocytosis, porcine respiratory and reproductive syndrome virus infection and the response to lipopolysaccharide stimulation. Furthermore, we performed transcriptome sequencing of the whole differentiation process to track the fate transitions of porcine PSCs involved in the signaling pathway. The activation of transforming growth factor beta signaling was required for the formation of mesoderm and the inhibition of the transforming growth factor beta signaling pathway at the hematopoietic endothelium stage could enhance the fate transformation of hematopoiesis. In summary, we developed an efficient and rapid protocol to generate pPSCdMs that showed aspects of functional maturity comparable with PAMs. pPSCdMs could provide a broad prospect for the platforms of host-pathogen interaction mechanisms.

摘要

从多能干细胞(PSCs)中获得的可再生猪源巨噬细胞资源将是宿主-病原体相互作用机制研究中替代原代猪肺泡巨噬细胞(PAMs)的有价值的选择。我们开发了一种高效、快速的方案,在 11 天内从猪 PSCs(pPSCs)中获得巨噬细胞。pPSC 衍生的巨噬细胞(pPSCdMs)表现出与原代巨噬细胞相似的分子和功能特征。pPSCdMs 表达巨噬细胞特异性表面蛋白和巨噬细胞特异性转录因子,与 PAMs 相似。pPSCdMs 还表现出巨噬细胞的功能特征,如内吞作用、吞噬作用、猪呼吸和繁殖综合征病毒感染以及对脂多糖刺激的反应。此外,我们对整个分化过程进行了转录组测序,以跟踪参与信号通路的猪 PSCs 的命运转变。转化生长因子β信号的激活对于中胚层的形成是必需的,而在造血内皮阶段抑制转化生长因子β信号通路可以增强造血的命运转变。总之,我们开发了一种高效、快速的方案来生成 pPSCdMs,其功能成熟度与 PAMs 相当。pPSCdMs 可为宿主-病原体相互作用机制的研究平台提供广阔的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee91/10825052/c69500a27c9c/gr1.jpg

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