Dorso-ventral heterogeneity in tracheal basal stem cells.

Dorso-ventral heterogeneity in tracheal basal stem cells.
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DOI:
10.1242/bio.058676
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发表时间:
2021-09-15
期刊:
影响因子:
2.4
通讯作者:
Taniguchi H
Taniguchi H
中科院分区:
生物学4区
文献类型:
--
作者:
Tadokoro T;Tanaka K;Osakabe S;Kato M;Kobayashi H;Hogan BLM;Taniguchi H

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气管基底细胞(BC)作为干细胞的功能,以维持上皮细胞的稳定状态,并在损伤后进行修复。气道腹外侧由软骨包围,背侧由平滑肌包围。使用Krt5-CreER的谱系追踪显示背侧BC比腹侧BC产生更多、更大的克隆。在软骨和平滑肌之间发现了大的克隆,其中存在背侧BCs亚群。BCs的三维类器官培养表明背侧BCs表现出比腹侧BCs更高的集落形成效率。基因本体分析显示,背侧BCs中表达的基因在伤口愈合中富集,而腹侧BCs在响应外部刺激和免疫应答中富集。值得注意的是,腹侧BC表达抑制平滑肌细胞生长的肌生长抑制素和促进软骨修复的HGF。这些结果支持了这一假设,即来自背腹气道的BC具有与其体内功能相关的内在分子和行为差异。总结:气管上皮的空间差异,特别是集中在基底干细胞的异质性,通过体内谱系追踪,组织学分析,气管球培养和基因本体分析来阐明。
The tracheal basal cells (BCs) function as stem cells to maintain the epithelium in steady state and repair it after injury. The airway is surrounded by cartilage ventrolaterally and smooth muscle dorsally. Lineage tracing using Krt5-CreER shows dorsal BCs produce more, larger, clones than ventral BCs. Large clones were found between cartilage and smooth muscle where subpopulation of dorsal BCs exists. Three-dimensional organoid culture of BCs demonstrated that dorsal BCs show higher colony forming efficacy to ventral BCs. Gene ontology analysis revealed that genes expressed in dorsal BCs are enriched in wound healing while ventral BCs are enriched in response to external stimulus and immune response. Significantly, ventral BCs express Myostatin, which inhibits the growth of smooth muscle cells, and HGF, which facilitates cartilage repair. The results support the hypothesis that BCs from the dorso-ventral airways have intrinsic molecular and behavioural differences relevant to their in vivo function. Summary: Spatial difference of tracheal epithelium, especially focused on the heterogeneity of basal stem cells, is elucidated by lineage tracing in vivo, histological analysis, tracheosphere culture, and gene ontology analysis.
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