CD9-positive cells in the intermediate lobe of the pituitary gland are important supplier for prolactin-producing cells in the anterior lobe
CD9-positive cells in the intermediate lobe of the pituitary gland are important supplier for prolactin-producing cells in the anterior lobe
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DOI：
10.1007/s00441-021-03460-5
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发表时间：
2021-05-07
影响因子：
3.6
通讯作者：
Ohsako, Shunji
中科院分区：
文献类型：
--
作者：
Horiguchi, Kotaro;Fujiwara, Ken;Ohsako, Shunji
来自干/祖细胞的垂体产生细胞的供应对于维持垂体的内分泌活动至关重要。在构成前叶和中叶（分别为AL和IL）的腺垂体中，表达性别决定区Y盒2（SOX 2）和S100 β的干细胞/祖细胞位于面向Rathke's裂（初级生态位）和实质的边缘细胞层（MCL）中AL（次级生态位）。我们以前的研究表明，四跨膜蛋白超家族CD 9和CD 81在原代和次级龛的S100 β/SOX 2阳性细胞（称为CD 9/CD 81/S100 β/SOX 2阳性细胞）中表达，位于AL侧龛的细胞具有可塑性和多能性。然而，目前尚不清楚IL侧原代小生境中的CD 9/CD 81/S100 β/SOX 2阳性细胞是否是AL或IL的干/祖细胞。在这里，我们成功地从IL-侧原代小生境中分离出纯的CD 9/CD 81/S100 β/SOX 2阳性细胞。与从AL中分离的CD 9/CD 81/S100 β/SOX 2阳性细胞相比，它们具有更高水平的S100 β和SOX 2 mRNA，以及更大的垂体球形成能力。它们还具有分化为所有类型的腺垂体瘤产生细胞的能力，伴随着CD 9表达的丧失。通过siRNA处理，CD 9/CD 81/S100 β/SOX 2阳性细胞中CD 9和CD 81功能的丧失损害了催乳素细胞分化。一致地，在CD 9/CD 81双敲除小鼠的垂体中，观察到MCL发育不全和催乳素细胞的较低群体。这些结果表明，IL侧MCL中的CD 9/CD 81/S100 β/SOX 2阳性细胞是AL中成体核心干细胞的潜在供应者。
A supply of hormone-producing cells from stem/progenitor cells is critical to sustain the endocrine activity of the pituitary gland. In the adenohypophysis composing the anterior and intermediate lobe (AL and IL, respectively), stem/progenitor cells expressing sex-determining region Y-box 2 (SOX2) and S100 beta are located in the marginal cell layer (MCL) facing Rathke's cleft (primary niche) and the parenchyma of the AL (secondary niche). Our previous studies using mice and rats indicated that the tetraspanin superfamily CD9 and CD81 are expressed in S100 beta/SOX2-positive cells of primary and secondary niches (named CD9/CD81/S100 beta/SOX2-positive cell), and the cells located in the AL-side niches exhibit plasticity and multipotency. However, it is unclear whether CD9/CD81/S100 beta/SOX2-positive cells in the IL-side primary niche are stem/progenitor cells for the AL or IL. Here, we successfully isolated pure CD9/CD81/S100 beta/SOX2-positive cells from the IL-side primary niche. They had a higher level of S100 beta and SOX2 mRNA and a greater pituisphere forming capacity than those of CD9/CD81/S100 beta/SOX2-positive cells isolated from the AL. They also had capacity to differentiate into all types of adenohypophyseal hormone-producing cells, concomitantly with the loss of CD9 expression. Loss of CD9 and CD81 function in CD9/CD81/S100 beta/SOX2-positive cells by siRNA treatment impaired prolactin cell differentiation. Consistently, in the pituitary gland of CD9/CD81 double knockout mice, dysgenesis of the MCL and a lower population of prolactin cells were observed. These results suggest that the CD9/CD81/S100 beta/SOX2-positive cells in the MCL of the IL-side are potential suppliers of adult core stem cells in the AL.