近日，中国科学院分子细胞科学卓越创新中心曾艺等研究人员合作发现，微环境炎症信号控制乳腺振荡再生并保护干细胞免受细胞毒性压力的影响。相关论文于2023年12月22日在线发表于国际学术期刊《细胞—干细胞》。

研究人员发现，细胞毒性应激诱导的CD11c⁺导管巨噬细胞活化有助于干细胞存活并防止分化。在发情周期中，这些巨噬细胞通过IL1β-IL1R1-NF-κB信号以振荡的方式促进Procr⁺乳腺干细胞（MaSC）的活性。在MaSC中删除IL1R1会导致干细胞损失和管腔分化偏向。此外，在化疗药物紫杉醇的细胞毒性压力下，导管巨噬细胞会分泌更高水平的IL1β，促进造血干细胞存活并阻止分化。

抑制IL1R1可使MaSC对紫杉醇敏感。这些研究结果揭示了一个调节再生的反复炎症过程，为压力诱导的炎症及其对干细胞存活的影响提供了见解，这可能会影响癌症疗法的疗效。

研究人员表示，众所周知，干细胞在应激后具有恢复力和更强的活性。在发情周期中，乳腺会经历频繁的重塑和反复的应激，但MaSC如何应对应激并促进再生仍不清楚。

附：英文原文

Title: Niche inflammatory signals control oscillating mammary regeneration and protect stem cells from cytotoxic stress

Author: Chunye Liu, Yishu Xu, Guowei Yang, Yu Tao, Jiali Chang, Shihui Wang, Tom H. Cheung, Jianfeng Chen, Yi Arial Zeng

Issue&Volume: 2023-12-22

Abstract: Stem cells are known for their resilience and enhanced activity post-stress. The mammarygland undergoes frequent remodeling and is subjected to recurring stress during theestrus cycle, but it remains unclear how mammary stem cells (MaSCs) respond to thestress and contribute to regeneration. We discovered that cytotoxic stress-inducedactivation of CD11c+ ductal macrophages aids stem cell survival and prevents differentiation. These macrophagesboost Procr+ MaSC activity through IL1β-IL1R1-NF-κB signaling during the estrus cycle in an oscillatingmanner. Deleting IL1R1 in MaSCs results in stem cell loss and skewed luminal differentiation.Moreover, under cytotoxic stress from the chemotherapy agent paclitaxel, ductal macrophagessecrete higher IL1β levels, promoting MaSC survival and preventing differentiation.Inhibiting IL1R1 sensitizes MaSCs to paclitaxel. Our findings reveal a recurring inflammatoryprocess that regulates regeneration, providing insights into stress-induced inflammationand its impact on stem cell survival, potentially affecting cancer therapy efficacy.

DOI: 10.1016/j.stem.2023.11.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00429-0