The analysis of differentiation into hormone-producing cells from stem/progenitor cells in rat anterior pituitary gland.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Kyorin University
• Principal Investigator: Horiguchi Kotaro 杏林大学, 保健学部, 准教授 (10409477)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 下垂体前葉 / CD9 / SOX2 / 組織幹細胞 / CD81 / 細胞表面抗原

Outline of Final Research Achievements

In the adenohypophysis composing the anterior and intermediate lobe (AL and IL), SOX2-positive cells located along the AL- and IL-side marginal cell layer (MCL) facing Rathke’s cleft, and the SOX2-positive cell clusters scattered throughout the parenchyma are proposed to act as the primary and secondary stem/progenitor cell niches, respectively. We identified the novel markers cluster of differentiation (CD) 9 and CD81 for the identification of S100β/SOX2-positive cells. Here, we first isolated pure CD9/SOX2-positive cells from the MCL of the IL-side. The CD9/SOX2-positive cells had a pituisphere forming capacity. They could differentiate into all types of adenohypophyseal hormone-producing cells. Consistently, dysgenesis of the MCL and a lower population of prolactin cells were observed in the pituitary gland of CD9/CD81 double knockout mice. These results suggest that the CD9/SOX2-positive cells in the MCL of the IL-side are potential suppliers of adult core stem cells in the AL.

Free Research Field

組織学

Academic Significance and Societal Importance of the Research Achievements

本研究では、ラット下垂体前葉の組織幹細胞がSOX2陽性細胞であることをCD9抗体を利用したビーズトラップ法によりCD9/SOX2陽性細胞の純化に成功し、様々な解析を行うことで証明した。そしてCD9/SOX2陽性細胞がin vitroにおいてホルモン産生細胞、及び血管内皮細胞への分化に成功した。さらに、血管内皮細胞への分化トリガーがケモカインであることを明らかにした。以上の結果は、下垂体前葉幹細胞からの細胞供給メカニズムの解明の一端となり、分化誘導した細胞塊を用いることで、臨床的に下垂体癌を治療する新たな方法への端緒になると考える。