Yoo, Kyusang Jo, Young-Woo Yoo, Takwon Hann, Sang-Hyeon Park, Inkuk Kim, Yea-Eun Kim, Ye Lynne Rhee, Joonwoo Song, In-Wook Kim, Ji-Hoon Baek, Daehyun Kong, Young-Yun 2024-10-26T06:30:37Z 2024-10-26T06:30:37Z 2024-10-25 2024-09 2050-084X https://pubs.kist.re.kr/handle/201004/150858 Fibro-adipogenic progenitors (FAPs) are muscle-resident mesenchymal progenitors that can contribute to muscle tissue homeostasis and regeneration, as well as postnatal maturation and lifelong maintenance of the neuromuscular system. Recently, traumatic injury to the peripheral nerve was shown to activate FAPs, suggesting that FAPs can respond to nerve injury. However, questions of how FAPs can sense the anatomically distant peripheral nerve injury and whether FAPs can directly contribute to nerve regeneration remained unanswered. Here, utilizing single-cell transcriptomics and mouse models, we discovered that a subset of FAPs expressing GDNF receptors Ret and Gfra1 can respond to peripheral nerve injury by sensing GDNF secreted by Schwann cells. Upon GDNF sensing, this subset becomes activated and expresses Bdnf. FAP-specific inactivation of Bdnf (Prrx1(Cre); Bdnf(fl/fl)) resulted in delayed nerve regeneration owing to defective remyelination, indicating that GDNF-sensing FAPs play an important role in the remyelination process during peripheral nerve regeneration. In aged mice, significantly reduced Bdnf expression in FAPs was observed upon nerve injury, suggesting the clinical relevance of FAP-derived BDNF in the age-related delays in nerve regeneration. Collectively, our study revealed the previously unidentified role of FAPs in peripheral nerve regeneration, and the molecular mechanism behind FAPs' response to peripheral nerve injury. English eLife Sciences Publications Muscle-resident mesenchymal progenitors sense and repair peripheral nerve injury via the GDNF-BDNF axis Article 10.7554/eLife.97662 1 eLife, v.13 eLife 13 Y scie scopus 001321498100001 2-s2.0-85204941049 Biology Life Sciences & Biomedicine - Other Topics Article FIBRO/ADIPOGENIC PROGENITORS STEM-CELLS REGENERATION EXPRESSION MYELINATION RECEPTOR FAMILY SCHWANN-CELLS SATELLITE CELLS SCIATIC-NERVE fibro-adipogenic progenitor single-cell RNA-sequencing schwann cell myelination peripheral nerve injury GDNF BDNF