Epimorphic regeneration in the mammalian tympanic membrane.

Epimorphic regeneration in the mammalian tympanic membrane.
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DOI:
10.1038/s41536-023-00332-0
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发表时间:
2023-10-18
影响因子:
7.2
通讯作者:
Tward, Aaron D.
Tward, Aaron D.
中科院分区:
医学1区
文献类型:
--
作者:
Scaria, Sonia M.;Frumm, Stacey M.;Vikram, Ellee P.;Easow, Sarah A.;Sheth, Amar H.;Shamir, Eliah R.;Yu, Shengyang Kevin;Tward, Aaron D.

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成年哺乳动物通常被认为再生复杂组织的能力有限,而是通过形成疤痕来修复伤口。在人类和跨哺乳动物物种中,鼓膜(TM)在没有干预的情况下快速修复穿孔。使用小鼠模型,我们证明了TM修复本身通过一个过程,承担了许多标志性的表型再生,而不是典型的伤口愈合。损伤后,TM形成以EGFR配体表达和信号传导为特征的伤口表皮。在从TM的已知干细胞区域出现的伤口表皮扩张后,募集多谱系胚细胞样细胞团。两周后,TM的组织结构基本恢复,但胶原蛋白紊乱。在接下来的几个月里,TM的组织化和图案化的胶原蛋白框架被恢复,从而导致无疤痕修复。最后,我们证明表皮中Egfr的缺失导致创伤表皮不能扩张,不能招募胚泡样细胞,不能再生正常的TM结构。这项工作建立了TM作为哺乳动物复杂组织再生的模型。
Adult mammals are generally believed to have limited ability to regenerate complex tissues and instead, repair wounds by forming scars. In humans and across mammalian species, the tympanic membrane (TM) rapidly repairs perforations without intervention. Using mouse models, we demonstrate that the TM repairs itself through a process that bears many hallmarks of epimorphic regeneration rather than typical wound healing. Following injury, the TM forms a wound epidermis characterized by EGFR ligand expression and signaling. After the expansion of the wound epidermis that emerges from known stem cell regions of the TM, a multi-lineage blastema-like cellular mass is recruited. After two weeks, the tissue architecture of the TM is largely restored, but with disorganized collagen. In the months that follow, the organized and patterned collagen framework of the TM is restored resulting in scar-free repair. Finally, we demonstrate that deletion of Egfr in the epidermis results in failure to expand the wound epidermis, recruit the blastema-like cells, and regenerate normal TM structure. This work establishes the TM as a model of mammalian complex tissue regeneration.
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