皮質オルガノイドの細胞ストレスは分子亜型の仕様を損なう
Aparna Bhaduri1,2, Madeline G Andrews1,2, Walter Mancia Leon2
1Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Nature
|January 31, 2020
まとめ
人間の脳オーガノイドは 発達中の脳皮質をモデルにしていますが 細胞の多様性や適切な細胞成熟が欠けているのです オーガノイドをマウスに移植することで 人間の脳の発達を研究する際に 精度が向上します
科学分野:
- 神経科学
- 発達生物学
- 幹細胞生物学
背景:
- 皮質オーガノイドは 人間の脳皮質の発達をモデル化した 3D 培養物です
- これらのオルガノイドモデルが 人間の脳の発達を 再現する確率は 未定です
研究 の 目的:
- 個々の原始的なヒト皮質細胞と皮質器官のトランスクリプトームを分析し,比較する.
- 人間の脳の発達モデリングにおける皮質器官の信頼性を評価する.
主な方法:
- 発達段階と領域におけるヒト皮質細胞の単細胞トランスクリプトーム解析
- 人間の皮質オルガノイドのトランスクリプトーム分析
- 皮質細胞とオルガノイドの間の遺伝子発現プロフィールの比較
- マウス皮質への移植後のオーガノイドの欠陥の評価
主要な成果:
- 人間の皮質の発達には,原始細胞の成熟,多様な細胞サブタイプ,および領域ニューロンの特異性があります.
- 皮質オルガノイドは広範な細胞クラスを示しますが,明確なサブタイプと適切なプロジェニター成熟が欠けています.
- 皮質領域の分子シグネチャーはオルガノイドニューロンに現れますが,空間的に組織されていません.
- オルガノイドはストレス経路を活性化し 細胞型特異性を損なうが 移植はこれらの欠陥を軽減する.
結論:
- 皮質オルガノイドは人間の脳の発達を部分的にモデル化しますが,細胞の多様性と成熟には限界があります.
- ネズミの脳への移植は 臓器の忠誠性を改善し ストレスに起因する欠陥を軽減します
- 開発されたデータセットとツールは,皮質オルガノイドの精度を評価し,強化するための枠組みを提供します.
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