Lgr5とLgr6で特徴づけられた解剖学的に機能的に異なる肺内膜群

Joo-Hyeon Lee¹, Tuomas Tammela², Matan Hofree³

¹Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.

Cell

|September 9, 2017

まとめ

研究者らはLgr5とLgr6を肺内膜細胞の主要なマーカーとして特定した. 滑らかな筋肉細胞を含むこれらの細胞は,呼吸道と胞上皮の再生と修復に不可欠です.

科学分野:

肺の生物学
幹細胞生物学
再生医療

背景:

肺内の特定のメゼンキマ細胞集団は,上皮の恒常状態と再生を調節し,大部分は特徴づけられていない.
これらの相互作用を理解することは,肺疾患の治療法の開発に不可欠です.

研究の目的:

大人の肺における新型のメゼンキマ細胞群を特定し,特徴づけること.
皮質の維持と修復におけるこれらの細胞の役割を解明する.

主な方法:

ネズミの遺伝子の追跡
単細胞RNAシーケンシング (scRNA-seq)
オーガノイド培養モデル

主要な成果:

Lgr5とLgr6は,典型的には幹細胞マーカーであり,肺の異なるメゼンキマ細胞サブ集団を識別する.
Lgr6+細胞は,Wnt-Fgf10シグナル伝達を通じて呼吸道上皮質の分化を促進する,呼吸道に関連した滑らかな筋肉細胞である.
Lgr5+細胞は膜領域に存在し,Wnt活性化によって膜上皮質の分化を促進する.
Lgr6+細胞の消去は,体内の呼吸道損傷の修復を阻害する.

結論:

Lgr5とLgr6は,肺上皮の恒常性および再生に不可欠な機能的に異なるメゼンキマ細胞をマークします.
Wntシグナル伝達によって媒介される地域特有のメゼンキマ・エピテリアの交響は,肺組織の維持を制御する.
これらの発見は肺の修復と再生における新しい細胞の役割とメカニズムを明らかにしています

キーワード:

信号は出ないアルベオラ上皮質ブロンチオール上皮区分する肺について肺幹細胞メゼンキマ細胞ニッチ

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