転写的景観における系統追跡は,分化過程で状態と運命を結びつける

Caleb Weinreb¹, Alejo Rodriguez-Fraticelli^2,3, Fernando D Camargo^2,3

¹Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)

|January 25, 2020

まとめ

研究者はDNAバーコードを使って細胞の発達を追跡し祖先細胞が成熟した細胞タイプになる方法を理解しましたこれは血液形成における早期の運命決定と単細胞の異なる分化経路を明らかにした.

科学分野:

発達生物学
細胞・分子生物学
血液形成の研究

背景:

先祖細胞の分子の違いと成熟した細胞の生成を関連付けることは重要な生物学的課題です
細胞運命を決定する仕組みを理解することは再生医療や病気の研究に不可欠です

研究の目的:

運命決定を研究するために,細胞のトランスクリプトームを時間とともに追跡する方法を開発し,適用する.
血液形成における分化可能性に関連する細胞状態を特定し,特徴づけること.
細胞の内在的な運命のバイアスを調査し,動的推論のための計算方法をベンチマークする.

主な方法:

時間の経過とともにトランスクリプトームのクローン追跡のための表現されたDNAバーコードを使用した.
単細胞RNA配列を解析し,細胞状態と転写パターンを分析した.
単細胞データから細胞動態を推論するためのベンチマーク計算アルゴリズム.

主要な成果:

連続したトランスクリプションの状況の中で, 運命の潜在的状態を特定した.
成熟した細胞に影響を与える2つの異なる単細胞の分化経路を発見した.
標準の単細胞RNA配列解析では検出できない細胞の内在的な運命のバイアスを明らかにしました
細胞の運命の決定は現在の最先端のアルゴリズムで検出されるより早く起こる

結論:

細胞運勢の動態を研究する強力なクローン追跡方法を開発した
血液形成における単細胞分化経路と早期の運命へのコミットメントに関する新しい洞察を提供した.
初期の細胞運命を決定し,正確な細胞動態を把握する現在の計算方法の限界を強調した.

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