小柯机器人

法国Asklepios生物制药公司Nathalie Cartier和巴黎大学Pierre-Marie Lledo、Kurt A. Sailor团队合作在研究中取得进展。他们发现造血干细胞移植(HSCT)化疗导致脑内小胶质细胞衰老和外周巨噬细胞浸入。相关论文于2022年2月21日发表在《自然-医学》杂志上。

研究人员发现HSCT化疗会严重破坏小鼠脑再生细胞群，包括成年神经发生的永久性丧失。小胶质细胞密度减半，导致小胶质细胞扩增，与许多衰老指标相吻合。尽管小胶质细胞表达细胞增殖标志物，但它们会在S期发生细胞周期停滞，其中大多数细胞表达衰老和抗凋亡标志物p21。在化疗结束恢复后对体内小胶质细胞的单细胞追踪显示其再生能力丧失，随后被供体巨噬细胞取代。研究人员发现HSCT化疗会导致小胶质细胞衰老，逐渐降低小胶质细胞密度至临界值，这为大脑外周巨噬细胞侵入提供了一个可能的生态位。

据了解，造血干细胞移植是一种用于治疗多种恶性和非恶性疾病的方法，而化疗用于移植前清髓。HSCT后大脑中包含外周移植的侵入巨噬细胞，尽管它们在正常个体大脑中不存在，但移植机制仍未确定。

附：英文原文

Title: Hematopoietic stem cell transplantation chemotherapy causes microglia senescence and peripheral macrophage engraftment in the brain

Author: Sailor, Kurt A., Agoranos, George, Lpez-Manzaneda, Sergio, Tada, Satoru, Gillet-Legrand, Beatrix, Guerinot, Corentin, Masson, Jean-Baptiste, Vestergaard, Christian L., Bonner, Melissa, Gagnidze, Khatuna, Veres, Gabor, Lledo, Pierre-Marie, Cartier, Nathalie

Issue&Volume: 2022-02-21

Abstract: Hematopoietic stem cell transplantation (HSCT) is a therapy used for multiple malignant and nonmalignant diseases, with chemotherapy used for pretransplantation myeloablation. The post-HSCT brain contains peripheral engrafted parenchymal macrophages, despite their absence in the normal brain, with the engraftment mechanism still undefined. Here we show that HSCT chemotherapy broadly disrupts mouse brain regenerative populations, including a permanent loss of adult neurogenesis. Microglial density was halved, causing microglial process expansion, coinciding with indicators of broad senescence. Although microglia expressed cell proliferation markers, they underwent cell cycle arrest in Sphase with a majority expressing the senescence and antiapoptotic marker p21. In vivo single-cell tracking of microglia after recovery from chemical depletion showed loss of their regenerative capacity, subsequently replaced with donor macrophages. We propose that HSCT chemotherapy causes microglial senescence with a gradual decrease to a critical microglial density, providing a permissive niche for peripheral macrophage engraftment of the brain.

DOI: 10.1038/s41591-022-01691-9

Source: https://www.nature.com/articles/s41591-022-01691-9

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex