ソマティック変異から推論されたヒト発達の広範な系統系

Tim H H Coorens¹, Luiza Moore^1,2, Philip S Robinson^1,3

¹Wellcome Sanger Institute, Hinxton, UK.

Nature

|August 26, 2021

まとめ

人間の体細胞は変異を蓄積し血統の追跡マーカーとして機能します早期の胚細胞分裂は,個体と組織間で変化し,成人の発達と生殖系統の起源に影響を及ぼし,重要な非対称性を示しています.

科学分野:

発達生物学
ゲノミクス
人間の生理学

背景:

体内の突然変異は生涯にわたって蓄積され,ジゴットから発生する.
共有された変異は細胞系統を辿るための自然なマーカーとして機能します
早期の人間の発達と組織パターンの理解は極めて重要です

研究の目的:

体の変異を用いてヒトの系統を再構築する
初期のヒト胚形成における発達不対称性の程度を調査する.
原始的な生殖細胞の起源とソマ-生殖細胞の発達分裂を調査する.

主な方法:

3人の成人の正常な組織からの511のレーザー捕獲マイクロ解剖の全ゲノムシーケンシング.
系統関係と発達史を推論する系統再構築
細胞の貢献と組織の空間的組織を決定するための変異パターンの分析.

主要な成果:

広範囲のフィロゲニーは,胚細胞の成人組織への貢献において,60:40から93:7の範囲の子細胞比率で,有意な非対称性を明らかにした.
発達不対称性は,次の細胞世代に浸透し,同じ個体内の異なる組織間で変化することが観察されました.
系統遺伝学的分析により,胚の空間的なパターンが解明され,単一の胚の祖先から派生した連続した組織パッチが特定され,原始生殖細胞への胚外的貢献が示唆された.

結論:

早期の胚細胞分裂は,大きく変化するアシンメトリーを示し,成人組織の構成とパターンを影響する.
胚形成の過程における系統的関与と発達上のボトルネックは,個体内および個体間の発達パターンの大きな変化につながります.
ソマティック突然変異に基づく系統は,発達史を再構築し,ヒトの組織発達を理解するための強力なツールを提供します.

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