Postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary gland.

Postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary gland.
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DOI:
10.1186/s13293-022-00467-7
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发表时间:
2022-10-11
影响因子:
7.9
通讯作者:
Wilson, Michael D.
Wilson, Michael D.
中科院分区:
医学2区
文献类型:
--
作者:
Hou, Huayun;Chan, Cadia;Yuki, Kyoko E.;Sokolowski, Dustin;Roy, Anna;Qu, Rihao;Uuskula-Reimand, Liis;Faykoo-Martinez, Mariela;Hudson, Matt;Corre, Christina;Goldenberg, Anna;Zhang, Zhaolei;Palmert, Mark R.;Wilson, Michael D.

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脑下垂体调节基本的生理过程,如生长、青春期开始、应激反应、代谢、生殖和哺乳。虽然性别偏见在这些功能和激素的生产已被描述,潜在的身份,时间部署,和细胞类型的特异性性别偏见的垂体基因调控网络还没有完全理解。为了捕捉出生后发育过程中垂体基因调控动力学的性别差异,我们进行了3'非翻译区测序和小RNA测序,以确定基因和microRNA表达分别在5个出生后年龄(出生后第12、22、27、32、37),其跨越雌性和雄性C57 BL/6 J小鼠垂体的青春期转变(每个年龄每个性别n = 5-6个生物学重复)。我们观察到超过900个性别偏向基因表达和17个性别偏向microRNA,其中大多数性别差异发生在青春期。使用miRNA-基因靶相互作用数据库,我们确定了18个性别偏向基因,这些基因是5个性别偏向microRNA的假定靶基因。此外,通过将我们的批量RNA-seq与公开可用的雄性和雌性小鼠垂体单核RNA-seq数据相结合,我们获得了细胞类型比例性别差异在青春期之前存在的证据,并且对于三种主要的促生长素产生细胞类型:促生长素,催乳素和促性腺激素,在青春期后持续存在。最后,我们确定了性别偏见的基因在这三种垂体细胞类型占细胞类型的性别之间的差异。我们的研究揭示了小鼠垂体性别偏向基因表达的身份和出生后发育轨迹。这项工作还强调了在理解脑垂体调节过程中的性别差异时,考虑细胞类型组成中的性别偏见的重要性。在线版本包含补充材料,可通过10.1186/s13293-022-00467-7获得。雄性和雌性小鼠垂体腺基因和miRNA表达在跨越青春期发育的5个出生后年龄中进行了分析。垂体基因表达的性别差异存在于青春期之前,并在青春期后变得更加突出。结合基因和miRNAs的表达数据,揭示了5种性别偏好miRNAs的18个推定的性别偏好基因靶标。生长激素、催乳激素和促性腺激素比例的性别差异预计在青春期之前出现。在线版本包含补充材料,可通过10.1186/s13293-022-00467-7获得。
The pituitary gland regulates essential physiological processes such as growth, pubertal onset, stress response, metabolism, reproduction, and lactation. While sex biases in these functions and hormone production have been described, the underlying identity, temporal deployment, and cell-type specificity of sex-biased pituitary gene regulatory networks are not fully understood. To capture sex differences in pituitary gene regulation dynamics during postnatal development, we performed 3’ untranslated region sequencing and small RNA sequencing to ascertain gene and microRNA expression, respectively, across five postnatal ages (postnatal days 12, 22, 27, 32, 37) that span the pubertal transition in female and male C57BL/6J mouse pituitaries (n = 5–6 biological replicates for each sex at each age). We observed over 900 instances of sex-biased gene expression and 17 sex-biased microRNAs, with the majority of sex differences occurring with puberty. Using miRNA–gene target interaction databases, we identified 18 sex-biased genes that were putative targets of 5 sex-biased microRNAs. In addition, by combining our bulk RNA-seq with publicly available male and female mouse pituitary single-nuclei RNA-seq data, we obtained evidence that cell-type proportion sex differences exist prior to puberty and persist post-puberty for three major hormone-producing cell types: somatotropes, lactotropes, and gonadotropes. Finally, we identified sex-biased genes in these three pituitary cell types after accounting for cell-type proportion differences between sexes. Our study reveals the identity and postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary. This work also highlights the importance of considering sex biases in cell-type composition when understanding sex differences in the processes regulated by the pituitary gland. The online version contains supplementary material available at 10.1186/s13293-022-00467-7. Male and female mouse pituitary gland gene and miRNA expression was profiled across five postnatal ages spanning pubertal development. Sex differences in pituitary gene expression exist prior to puberty and become more prominent upon puberty. Combining expression data from genes and miRNAs revealed 18 putative sex-biased gene targets of 5 sex-biased miRNAs. Sex differences in the proportions of somatotropes, lactotropes, and gonadotropes are predicted to occur prior to puberty. The online version contains supplementary material available at 10.1186/s13293-022-00467-7.
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