State Key Laboratory of Swine and Poultry Breeding Industry & Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition &, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China.
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
BMC Genomics. 2024 May 20;25(1):494. doi: 10.1186/s12864-024-10398-9.
Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development.
In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment.
These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.
乳腺发育是哺乳动物的一个关键过程，对其生殖成功和后代营养至关重要。然而，与乳头数量相关的关键候选基因（包括 ABCD4、VRTN、PROX2 和 DLST）在这个发育过程中的功能作用仍不清楚。为了填补这一知识空白，我们深入研究了这些候选基因在小鼠乳腺发育过程中的动态表达模式、功能意义和调控网络。
在这项研究中，我们描述了关键基因在乳腺发育中的时空表达模式。使用时间序列单细胞数据，我们揭示了在胚胎和成年阶段乳腺细胞群体中 A bcd4、Vrtn、Prox2 和 Dlst 的表达存在差异，而 Vrtn 在任何细胞中都未检测到。我们发现，只有 Abcd4 的过表达和敲低才能抑制 HC11 乳腺上皮细胞的增殖并促进其凋亡，而 Prox2 和 Dlst 对这些细胞没有显著影响。通过 RNA-seq 和 qPCR 进一步分析表明，Abcd4 可以诱导参与乳腺发育的基因表达水平的广泛变化，如 Igfbp3、Ccl5、Tlr2 和 Prlr 等，这些基因主要与 MAPK、JAK-STAT 和 PI3K-AKT 途径相关，这是通过功能富集得到的。
这些发现表明 ABCD4 是一个候选基因，通过影响 PRLR 的表达，在妊娠期间调节乳腺发育和泌乳。
