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全面的 CRISPR-Cas9 筛选确定了对浆母细胞发育重要的因素。

Comprehensive CRISPR-Cas9 screen identifies factors which are important for plasmablast development.

机构信息

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, Vienna, Austria.

出版信息

Front Immunol. 2022 Sep 15;13:979606. doi: 10.3389/fimmu.2022.979606. eCollection 2022.

Abstract

Plasma cells (PCs) and their progenitors plasmablasts (PBs) are essential for the acute and long-term protection of the host against infections by providing vast levels of highly specific antibodies. Several transcription factors, like Blimp1 and Irf4, are already known to be essential for PC and PB differentiation and survival. We set out to identify additional genes, that are essential for PB development by CRISPR-Cas9 screening of 3,000 genes for the loss of PBs by employing the -inducible germinal center B cell (iGB) culture system and Rosa26 mice. Identified hits in the screen were and , which are known to contribute to the loop extrusion function of the cohesin complex. Other examples of promising hits were , , and . We thus provide a new set of genes, which are important for PB development.

摘要

浆细胞(PCs)及其前体细胞浆母细胞(PBs)通过提供大量高度特异性的抗体,对于宿主对抗感染的急性和长期保护至关重要。几种转录因子,如 Blimp1 和 Irf4,已经被证明对 PC 和 PB 的分化和存活是必不可少的。我们通过使用 - 诱导的生发中心 B 细胞(iGB)培养系统和 Rosa26 小鼠,对 3000 个基因进行 CRISPR-Cas9 筛选,以寻找 PB 缺失的必需基因,从而确定了另外一些对 PB 发育至关重要的基因,这些基因参与了黏着蛋白复合物的环挤出功能。其他有希望的命中靶点包括、和。因此,我们提供了一组对 PB 发育很重要的新基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9cf/9521597/eb83709774cc/fimmu-13-979606-g001.jpg

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