Identification of adreno-gonadal primordium from human iPSC and elucidation of its differentiation pathway

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09880
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kyoto University
• Principal Investigator: Sone Masakatsu 京都大学, 医学研究科, 特定准教授 (40437207)
• Co-Investigator(Kenkyū-buntansha): 田浦 大輔 京都大学, 医学研究科, 特定助教 (10558612)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: adrenal / gonad / iPS

Outline of Final Research Achievements

We tried to elucidate the steroidogenic differentiation processes using hiPSC-derived intermediate mesoderm (IM) that is known to be the origin of the human adrenal cortex and gonads. IM cells expressing Odd-skipped related 1 (OSR1), an early IM marker, were sorted and transfected with steroidogenic factor-1 (SF-1) /adrenal 4 binding protein. Analysis of OSR1+ cells transfected with SF-1 revealed that dopamine D1 receptor agonist upregulated expression of various steroidogenic enzymes and increased secretion of steroid hormones synergistically with adrenocorticotropic hormone. These OSR1+ cells transfected with SF-1 secreted both gonadal and adrenal steroid hormones. 3-dimensional culture of these cells upregulated the expression of various steroidogenic enzymes. We are now trying to elucidate the mechanism of organ-specific differentiation into gonadal cells and adrenocortical cells.

Free Research Field

内分泌代謝

Academic Significance and Societal Importance of the Research Achievements

我々は、世界で初めてヒトiPS細胞から中間中胚葉を経て副腎皮質ステロイド産生細胞を誘導することに成功しており、本研究はその手法のさらなる発展とin vitroでの発生研究への応用を目指したものである。ヒトiPS細胞を利用することによりヒトの発生・分化メカニズムをin vitroで解明することを目指したもので学術的意義は高く、また将来の副腎・性腺の再生療法への応用も考えられるため社会的意義も高い。