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プロゲステロン受容体によるヒト心臓の成熟の性別制御
Choon Boon Sim1,2, Belinda Phipson1,3, Mark Ziemann4,5,6
1Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
Circulation
|March 8, 2021
まとめ
プロゲステロン受容体は,胎児期から成人期までの代謝および収縮性特性に影響し,性別の人間の心臓の成熟に不可欠である. この発見は 心臓の発達と 潜在的治療目標の 洞察を与えてくれます
科学分野:
- 心血管生物学
- 発達生物学
- ゲノミクス
背景:
- 胎児の心臓の発達はよく知られていますが 胎児の心臓の成熟のシグナルについては ほとんど知られていません
- 生後心臓の成熟を 理解することは 生涯にわたる 心臓病の治療に不可欠です
研究 の 目的:
- 人間の心臓の成熟過程における転写とクロマチンのアクセシビリティの変化をプロファイルする.
- 性別特異的な心臓発達の主要な分子媒介者を特定する.
主な方法:
- 9人のヒトドナーの54,140個の核の単核RNA配列化 (snRNA-seq).
- 精製された心筋細胞核の配列化 (ATAC-seq) を用いた大量RNA配列化とトランスポゼアクセシブルクロマチンの測定.
- 人間の心臓器官とマウスモデルでの機能的検証
主要な成果:
- プロゲステロン受容体は,心筋細胞の成熟期における性依存の転写プログラムの主な媒介体として特定された.
- プロゲステロン受容体が 性別特有の代謝プログラムと 心臓の収縮性特性の成熟を 誘導することを示した.
- 人間の心臓の成熟に関連した 異なった転写とクロマチンのアクセシビリティの風景を明らかにした.
結論:
- プロゲステロン受容体は 人間の心臓の発達と成熟に 重要な役割を果たします
- これらの発見は,性別の人間の心臓の成熟を理解するための包括的な青写真を提供します.
- 心臓の発達と疾患に 標的を絞った介入の道を開きます
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