Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
School of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Endocrinology. 2023 Apr 17;164(6). doi: 10.1210/endocr/bqad076.
The pituitary gland regulates growth, metabolism, reproduction, the stress response, uterine contractions, lactation, and water retention. It secretes hormones in response to hypothalamic input, end organ feedback, and diurnal cues. The mechanisms by which pituitary stem cells are recruited to proliferate, maintain quiescence, or differentiate into specific cell types, especially thyrotropes, are not well understood. We used single-cell RNA sequencing in juvenile P7 mouse pituitary cells to identify novel factors in pituitary cell populations, with a focus on thyrotropes and rare subtypes. We first observed cells coexpressing markers of both thyrotropes and gonadotropes, such as Pou1f1 and Nr5a1. This was validated in vivo by both immunohistochemistry and lineage tracing of thyrotropes derived from Nr5a1-Cre; mTmG mice and demonstrates that Nr5a1-progenitors give rise to a proportion of thyrotropes during development. Our data set also identifies novel factors expressed in pars distalis and pars tuberalis thyrotropes, including the Shox2b isoform in all thyrotropes and Sox14 specifically in Pou1f1-negative pars tuberalis thyrotropes. We have therefore used single-cell transcriptomics to determine a novel developmental trajectory for thyrotropes and potential novel regulators of thyrotrope populations.
垂体调节生长、代谢、生殖、应激反应、子宫收缩、泌乳和水潴留。它根据下丘脑的输入、终末器官的反馈和昼夜节律线索分泌激素。垂体干细胞被招募来增殖、保持静止或分化为特定细胞类型（尤其是促甲状腺细胞）的机制尚不清楚。我们使用幼年 P7 期小鼠垂体细胞的单细胞 RNA 测序来鉴定垂体细胞群体中的新因子，重点是促甲状腺细胞和罕见亚型。我们首先观察到细胞共表达促甲状腺细胞和促性腺激素细胞的标志物，如 Pou1f1 和 Nr5a1。这在体内通过 Nr5a1-Cre；mTmG 小鼠的免疫组织化学和源于该小鼠的促甲状腺细胞的谱系追踪得到了验证，并表明 Nr5a1 祖细胞在发育过程中产生了一部分促甲状腺细胞。我们的数据集还鉴定了在垂体远侧部和垂体中间部促甲状腺细胞中表达的新因子，包括所有促甲状腺细胞中的 Shox2b 同工型和 Pou1f1 阴性垂体中间部促甲状腺细胞中的 Sox14。因此，我们使用单细胞转录组学来确定促甲状腺细胞的新发育轨迹和促甲状腺细胞群体的潜在新调节因子。
