Neonatal epicardial-derived progenitors aquire myogenic traits in skeletal muscle, but not cardiac muscle

详细信息    查看全文

• 作者：Ditte C. Andersen^a ; ^b ; ^d ; ^{dandersen@health.sdu.dk" class="auth_mail" title="E-mail the corresponding author} ; Charlotte H. Jensen^a ; ^d ; Ida Skovrind^a ; ^b ; ^d ; Rikke Helin Johnsen^a ; ^b ; ^d ; Gunnhildur Asta Traustadottir^a ; ^c ; ^d ; Katrine S. Aagaard^a ; ^c ; ^d ; Suganya Ganesalingam^a ; ^c ; ^d ; Sø ; ren P. Sheikh^a ; ^c ; ^d
• 关键词：Epicardial progenitors ; Stem cell transplantation ; Heart infarct ; Mouse ; Regenerating skeletal muscle ; Myogenic specification
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：1 November 2016
• 年：2016
• 卷：222
• 期：Complete
• 页码：448-456
• 全文大小：3213 K

文摘

Epicardium-derived progenitor cells (EPDCs) differentiate into all heart cell types in the embryonic heart, yet their differentiation into cardiomyocytes in the adult heart is limited and poorly described. This may be due to EPDCs lacking myogenic potential or the inert adult heart missing regenerative signals essential for directed differentiation of EPDCs. Herein, we aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal mouse myocardium, as well as in skeletal muscle. The two latter tissues have an intrinsic capability to develop and regenerate, in contrast to the adult heart.

Methods

Highly purified mouse EPDCs were transplanted into damaged neonatal and adult myocardium as well as regenerating skeletal muscle. Co-cultures with skeletal myoblasts were used to distinguish fusion independent myogenic conversion.

Results

No donor EPDC-derived cardiomyocytes were observed in hearts. In contrast, a remarkable contribution of EPDCs to skeletal muscle myofiber formation was evident m>in vivom>. Furthermore, co-cultures of EPDCs with myoblasts showed that EPDCs became part of multinucleated fibers and appeared to acquire myogenic traits independent of a fusion event. Fluorescence activated cell sorting of EPDCs co-cultured with and without myoblasts and subsequent qRT-PCR of 64 transcripts established that the myogenic phenotype conversion was accomplished through induction of a transcriptional myogenic program.

Conclusion

These results suggest that EPDCs may be more myogenic than previously anticipated. But, the heart may lack factors for induction of myogenesis of EPDCs, a scenario that should be taken into consideration when aiming for repair of damaged myocardium by stem cell transplantation.