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Publications of the Week

Adaptations in Hippo-Yap Signaling and Myofibroblast Fate Underlie Scar-Free Ear Appendage Wound Healing in Spiny Mice

By October 14, 2021No Comments

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This week we profile a recent publication in Developmental Cell from the laboratories of Drs. Mark Majesky (pictured, left), Kathleen Millen (center), and Branden Nelson (right) at Seattle Children’s.

Can you provide a brief overview of your lab’s current research focus?

This work is the result of an interdisciplinary collaboration between multiple scientists at Seattle Children’s Research Institute with developmental biology, regenerative biology and molecular biology expertise. Although all of us have had a central focus on other biological problems, examining the fundamental mechanisms driving the extraordinary regenerative properties of Acomys (Spiny mice) brought us together. 

We are currently dissecting the molecular and cellular mechanisms of regenerative healing in multiple systems, including kidney and brain to define how Acomys maintain a healthy lifespan.

What is the significance of the findings in this publication?

Most mammalian species exhibit scar-free wound repair during fetal or early post-natal development. However, this ability is lost shortly after birth, transitioning to a scar-forming fibrotic response to tissue injuries. Indeed, progressive fibrosis underlies many degenerative diseases, including cardiac failure, idiopathic pulmonary disease, chronic kidney disease, liver cirrhosis and scleroderma. Regrettably, few treatments exist for patients with these end-stage fibrotic diseases other than organ transplantation. Unlike most mammals, Acomys have the extraordinary ability to heal tissue by regenerative wound healing instead of scarring as adults, even with age. 

We report the first cellular and molecular mechanisms linking evolved adaptations in Yap-TEAD signaling to the tissue regenerative wound healing properties in Spiny mice. By learning how these animals naturally accomplish this, we aim to identify new therapeutics for human wound healing.

What are the next steps for this research?

Our long-term goal is to develop pro-regenerative anti-fibrosis treatments for human injuries and diseases.

If you’d like us to mention your funding sources, please list them.

The majority of work was supported by a grant from the W.M. Keck Foundation. Additional support was provided by NIH grants (RO1-DK114149, RO1-HL123650, R21-OD023838, U24-DK115255, and T32-HL007312); from the Loie Power Robinson Stem Cell & Regenerative Medicine Fund, Seattle Children’s Research Institute and the Seattle Children’s Foundation.

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