Regulation of cellular lineages by PAX2 during kidney development

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03699
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kumamoto University
• Principal Investigator: Kobayashi Akio 熊本大学, 発生医学研究所, 准教授 (90840223)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腎臓発生 / 前駆細胞 / 細胞系譜境界 / ネフロン / PAX2

Outline of Final Research Achievements

It is currently unclear how cellular linages are formed during kidney development in mammals. We previously discovered that the cellular lineage boundary between the nephron and renal interstitium is established by PAX2 function in nephron progenitor cells repressing renal interstitial cell fates in the mouse. Here, we showed that this PAX2 function regulating the nephron-interstitium lineage boundary is restricted to nephron progenitor cells and is lost upon initiation of nephron differentiation. We further found that the requirement of PAX2 function can be recapitulated in nephron organoids generated from induced pluripotent stem (iPS) cells.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

哺乳類の腎臓発生における細胞系譜境界形成の機構は不明であるが、本研究成果であるPAX2機能を手がかりに、細胞系譜境界の形成メカニズムを解き明かせる可能性が開けた。またヒト腎臓オルガノイドを用いてヒトPAX2変異であるRenal coloboma syndrome (RCS)の疾患モデルを確立することで、より良い再生医療ための知識の基礎を築き、将来的に透析・腎移植の必要性を無くし、RCSを含む腎臓病患者やその家族の負担を軽減することに繋がると期待される。