Tissue-resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice
Tissue-resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice
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DOI：
10.7554/elife.57438
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发表时间：
2020-06-01
期刊：
影响因子：
7.7
通讯作者：
Schwertfeger, Kathryn L.
中科院分区：
文献类型：
--
作者：
Wang, Ying;Chaffee, Thomas S.;Schwertfeger, Kathryn L.
乳腺中的组织驻留巨噬细胞与上皮结构和脂肪基质内密切相关，对乳腺发育和组织动态平衡具有重要作用。巨噬细胞与处女乳腺导管发育有关，但对巨噬细胞对脂肪间质的影响知之甚少。使用转录图谱和单细胞RNA测序方法，我们在未分娩的小鼠乳腺中鉴定了一个独特的驻留基质巨噬细胞亚群，其特征是Lyve-1的表达，Lyve-1是细胞外基质(ECM)成分透明质酸的受体。这一亚群富含与细胞外基质重塑相关的基因，并与处女乳腺的脂肪基质和纤维包膜内的透明质酸富集区特异性相关。此外，巨噬细胞的耗尽导致脂肪相关间质中透明质酸相关ECM的聚集增加，这表明驻留的巨噬细胞对于维持未分娩的乳腺间质内的动态平衡非常重要。
Tissue-resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. Macrophages have been linked to ductal development in the virgin mammary gland, but less is known regarding the effects of macrophages on the adipose stroma. Using transcriptional profiling and single-cell RNA sequencing approaches, we identify a distinct resident stromal macrophage subpopulation within the mouse nulliparous mammary gland that is characterized by the expression of Lyve-1, a receptor for the extracellular matrix (ECM) component hyaluronan. This subpopulation is enriched in genes associated with ECM remodeling and is specifically associated with hyaluronan-rich regions within the adipose stroma and fibrous capsule of the virgin mammary gland. Furthermore, macrophage depletion leads to enhanced accumulation of hyaluronan-associated ECM in the adipose-associated stroma, indicating that resident macrophages are important for maintaining homeostasis within the nulliparous mammary gland stroma.