ヒト特有の脳進化のモデルとして脳オルガノイドを確立する

Alex A Pollen¹, Aparna Bhaduri¹, Madeline G Andrews¹

¹Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, UCSF, San Francisco, CA, USA.

Cell

|February 9, 2019

まとめ

人間の脳の発達には独特の分子の経路があります PI3K-AKT-mTORのような人間の皮質の発達に特異的な遺伝子や信号伝達経路を特定するために脳器官を用いました

科学分野:

神経科学
発達生物学
進化生物学

背景:

人間の脳とヒト以外の霊長類の脳を直接比較することは人間の脳の特異性を理解する上で極めて重要です
チンパンジーの脳組織は重要な新皮質の発達段階では利用できず早期の脳の大きさの違いに関する研究を妨げています

研究の目的:

皮質の発達におけるヒト特有の分子特性を特定する.
人間の脳の進化に寄与する分子変化を分析するためのプラットフォームを確立する.

主な方法:

チンパンジーの多能幹細胞から作られた脳器官
人間とチンパンジーのオルガノイドとマカクの皮質の遺伝子発現を比較した.
PI3K-AKT-mTOR信号経路の活性化を分析した.

主要な成果:

オルガノイドモデルは代謝の違いにもかかわらず重要な遺伝子規制ネットワークを保存した.
ヒトとチンパンジーのオルガノイドとマカクの皮質で異なった発現する261の遺伝子を特定し,最近の遺伝子複製に富んだ.
人体特有の受容体INSRとITGB8に依存するPI3K- AKT- mTOR経路の活性化が観察された.

結論:

人間の脳オーガノイドは,人間特有の脳の発達を研究するための実用的なモデルを提供します.
最近の遺伝子複製と,INSRとITGB8によって調節されるPI3K-AKT-mTOR経路は,ヒトの皮質進化に関与しています.

キーワード:

脳の器官チンパンジー皮質の発達人間特有の進化 mTOR についてマカークニューラルプロジェニター細胞ラディアル・グリア単細胞RNAシーケンシング

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