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脂肪细胞衍生的氨基酸储存蛋白是成年雌性生殖系干细胞维持所必需的。

Adipocyte-Derived Amino Acid Storage Proteins are Required for Germline Stem Cell Maintenance in Adult Females.

作者信息

Zike Anna B, Abel Madison G, Eisman Robert C, Weaver Lesley N

机构信息

Department of Biology, Indiana University, Bloomington, IN 47405, USA.

出版信息

bioRxiv. 2025 Aug 25:2025.08.24.672014. doi: 10.1101/2025.08.24.672014.

Abstract

Tissue homeostasis is dependent on precise coordination between endocrine organs in response to changes in organism physiology. Secreted circulating factors from adipocytes (called adipokines) regulate the behavior of stem cell lineages in peripheral tissues in multiple organisms. In addition to their endocrine roles, adipocytes store and secrete amino acid storage proteins throughout development. During the larval feeding period, adipocytes secrete storage proteins into the hemolymph, which are reabsorbed by the adipose tissue during metamorphosis to control adult organ size and fertility. Despite the known functions for storage proteins during the larval stages, their requirement during adulthood and reproduction are uncharacterized. We discover that adipocyte-specific knockdown of the storage proteins () and () results in a decrease in GSC maintenance. We further reveal that decreased GSC number is due to downregulation of Target of Rapamycin (TOR) signaling in GSCs, suggesting compromised amino acid sensing directly in GSCs. We also find that the proteins that mediate storage protein adipocyte reabsorption, Fat body protein 1 (Fbp1) and Fat body protein 2 (Fbp2), are expressed in ovarian follicle cells. Intriguingly, Fbp1 nor Fbp2 appear to be required in follicle cells for GSC maintenance, suggesting undiscovered requirements for amino acid storage proteins in oogenesis. Our results highlight a novel role for amino acid storage proteins during adulthood and in regulating tissue stem cell lineages.

摘要

组织稳态依赖于内分泌器官之间的精确协调,以响应机体生理变化。脂肪细胞分泌的循环因子(称为脂肪因子)调节多种生物体外周组织中干细胞谱系的行为。除了其内分泌作用外,脂肪细胞在整个发育过程中储存和分泌氨基酸储存蛋白。在幼虫摄食期,脂肪细胞将储存蛋白分泌到血淋巴中,在变态过程中被脂肪组织重新吸收,以控制成虫器官大小和生育能力。尽管已知储存蛋白在幼虫阶段的功能,但其在成年期和繁殖过程中的需求尚不清楚。我们发现,脂肪细胞特异性敲低储存蛋白()和()会导致生殖干细胞维持能力下降。我们进一步揭示,生殖干细胞数量减少是由于生殖干细胞中雷帕霉素靶蛋白(TOR)信号通路下调,这表明生殖干细胞中氨基酸感知功能受损。我们还发现,介导储存蛋白被脂肪细胞重新吸收的蛋白,脂肪体蛋白1(Fbp1)和脂肪体蛋白2(Fbp2),在卵巢卵泡细胞中表达。有趣的是,卵泡细胞中似乎不需要Fbp1和Fbp2来维持生殖干细胞,这表明在卵子发生过程中对氨基酸储存蛋白有未被发现的需求。我们的结果突出了氨基酸储存蛋白在成年期和调节组织干细胞谱系中的新作用。

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