Age, sex, and cell type-resolved hypothalamic gene expression across the pubertal transition in mice.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Dustin J Sokolowski, Huayun Hou, Kyoko E Yuki, Anna Roy, Cadia Chan, Wendy Choi, Mariela Faykoo-Martinez, Matt Hudson, Christina Corre, Liis Uusküla-Reimand, Anna Goldenberg, Mark R Palmert, Michael D Wilson
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Abstract

Background: The hypothalamus plays a central role in regulating puberty. However, our knowledge of the postnatal gene regulatory networks that control the pubertal transition in males and females is incomplete. Here, we investigate the age-, sex- and cell-type-specific gene regulation in the hypothalamus across the pubertal transition.

Methods: We used RNA-seq to profile hypothalamic gene expression in male and female mice at five time points spanning the onset of puberty (postnatal days (PD) 12, 22, 27, 32, and 37). By combining this data with hypothalamic single nuclei RNA-seq data from pre- and postpubertal mice, we assigned gene expression changes to their most likely cell types of origin. In our colony, pubertal onset occurs earlier in male mice, allowing us to focus on genes whose expression is dynamic across ages and offset between sexes, and to explore the bases of sex effects.

Results: Our age-by-sex pattern of expression enriched for biological pathways involved hormone production, neuronal activation, and glial maturation. Additionally, we inferred a robust expansion of oligodendrocytes precursor cells into mature oligodendrocytes spanning the prepubertal (PD12) to peri-pubertal (PD27) timepoints. Using spatial transcriptomic data from postpubertal mice, we observed the lateral hypothalamic area and zona incerta were the most oligodendrocyte-rich regions and that these cells expressed genes known to be involved in pubertal regulation.

Conclusion: Together, by incorporating multiple biological timepoints and using sex as a variable, we identified gene and cell-type changes that may participate in orchestrating the pubertal transition and provided a resource for future studies of postnatal hypothalamic gene regulation.

跨越小鼠青春期过渡期的年龄、性别和细胞类型分辨的下丘脑基因表达。
背景:下丘脑在调控青春期方面发挥着核心作用。然而,我们对控制男性和女性青春期过渡的产后基因调控网络的了解并不全面。在此,我们研究了青春期过渡时期下丘脑中年龄、性别和细胞类型特异性的基因调控:方法:我们使用 RNA-seq 分析了雄性和雌性小鼠在青春期开始的五个时间点(出生后第 12、22、27、32 和 37 天)的下丘脑基因表达。通过将这些数据与来自青春期前后小鼠的下丘脑单个核RNA-seq数据相结合,我们将基因表达变化归因于其最可能的起源细胞类型。在我们的小鼠群中,雄性小鼠的青春期来临较早,这使我们能够集中研究在不同年龄段和不同性别间表达动态变化的基因,并探索性别效应的基础:结果:我们按性别划分的年龄表达模式富集了涉及激素分泌、神经元激活和神经胶质成熟的生物通路。此外,我们还推断出少突胶质细胞前体细胞向成熟少突胶质细胞的强劲扩张跨越了青春期前(PD12)到青春期前后(PD27)的时间点。利用发育后小鼠的空间转录组数据,我们观察到下丘脑外侧区和内侧区是少突胶质细胞最丰富的区域,而且这些细胞表达了已知参与青春期调控的基因:总之,通过结合多个生物学时间点和使用性别作为变量,我们确定了可能参与协调青春期过渡的基因和细胞类型变化,并为今后研究出生后下丘脑基因调控提供了资源。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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