Smiljanic Kosara, Constantin Stephanie, Nessa Naseratun, Stojilkovic Stanko S
Section on Cellular Signaling, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
bioRxiv. 2025 Jun 6:2025.06.03.657631. doi: 10.1101/2025.06.03.657631.
Postnatal differentiation of gonadotrophs from Sox2-expressing stem cells is essential for maturation of the hypothalamic-pituitary-gonadal axis, puberty, and reproduction. Here, we examined the differentiation and maintenance of gonadotrophs in developing and adult female mice. Gonadotrophs and Sox2-expressing cells were visualized by immunostaining, and gonadotrophs were also identified by specific expression of the fluorescent protein tdTomato during embryonic and postnatal development. Sox2-expressing cells are localized in the anterior parenchyma, marginal zone, and posterior pituitary, regardless of mouse age. Gonadotrophs are localized in the anterior parenchyma distinct from Sox2-expressing cells. During the juvenile and prepubertal periods, cells in transition from Sox2 expression to the tdTomato expression, as well as numerous differentiated gonadotrophs, were also present in the marginal zone. The size and distribution of newly differentiated gonadotrophs was consistent with their maturation and migration into parenchyma. Specific knockout of PI4 kinase A in gonadotrophs disrupted their postnatal differentiation in the marginal zone, causing a significant reduction in the size of the gonadotroph population. This was accompanied by a progressive loss of gonadotroph-specific gene/protein expression and an increase in the number of regressed tdTomato-expressing cells. Thus, cells expressing Sox2 in the marginal zone, but not in the parenchyma, serve as stem cells for postnatal gonadotrophs, and the differentiation and maintenance of these cells require PI4 kinase A-derived phosphoinositides.
从表达Sox2的干细胞中分化出促性腺激素细胞对于下丘脑 - 垂体 - 性腺轴的成熟、青春期和生殖至关重要。在此，我们研究了发育中和成年雌性小鼠中促性腺激素细胞的分化和维持情况。通过免疫染色观察促性腺激素细胞和表达Sox2的细胞，并且在胚胎期和出生后发育过程中，还通过荧光蛋白tdTomato的特异性表达来鉴定促性腺激素细胞。无论小鼠年龄如何，表达Sox2的细胞都位于前叶实质、边缘区和垂体后叶。促性腺激素细胞位于与表达Sox2的细胞不同的前叶实质中。在幼年和青春期前阶段，边缘区也存在从表达Sox2向表达tdTomato转变的细胞以及众多分化的促性腺激素细胞。新分化的促性腺激素细胞的大小和分布与它们的成熟和向实质的迁移一致。在促性腺激素细胞中特异性敲除PI4激酶A会破坏它们在边缘区的出生后分化，导致促性腺激素细胞群体大小显著减少。这伴随着促性腺激素特异性基因/蛋白表达的逐渐丧失以及表达tdTomato的退化细胞数量增加。因此，边缘区而非实质中表达Sox2的细胞作为出生后促性腺激素细胞的干细胞，并且这些细胞的分化和维持需要PI4激酶A衍生的磷酸肌醇。
