A conserved HH-Gli1-Mycn network regulates heart regeneration from newt to human
| Autor: | Naoko Koyano-Nakagawa, Bhairab N. Singh, Cyprian Weaver, Ivan P. Moskowitz, Satyabrata Das, Wuming Gong, Mary G. Garry, Elizabeth A. Braunlin, Jop H. van Berlo, Daniel J. Garry |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hh signaling animal structures Science General Physics and Astronomy Zinc Finger Protein GLI1 General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences GLI1 medicine Animals Humans Regeneration Mrna transfection Hedgehog Proteins Myocytes Cardiac lcsh:Science Hedgehog Cell Proliferation N-Myc Proto-Oncogene Protein Multidisciplinary Biological studies biology Regeneration (biology) Heart General Chemistry medicine.disease Salamandridae Cell biology 030104 developmental biology Heart failure embryonic structures biology.protein lcsh:Q Function (biology) Signal Transduction |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-18 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The mammalian heart has a limited regenerative capacity and typically progresses to heart failure following injury. Here, we defined a hedgehog (HH)-Gli1-Mycn network for cardiomyocyte proliferation and heart regeneration from amphibians to mammals. Using a genome-wide screen, we verified that HH signaling was essential for heart regeneration in the injured newt. Next, pharmacological and genetic loss- and gain-of-function of HH signaling demonstrated the essential requirement for HH signaling in the neonatal, adolescent, and adult mouse heart regeneration, and in the proliferation of hiPSC-derived cardiomyocytes. Fate-mapping and molecular biological studies revealed that HH signaling, via a HH-Gli1-Mycn network, contributed to heart regeneration by inducing proliferation of pre-existing cardiomyocytes and not by de novo cardiomyogenesis. Further, Mycn mRNA transfection experiments recapitulated the effects of HH signaling and promoted adult cardiomyocyte proliferation. These studies defined an evolutionarily conserved function of HH signaling that may serve as a platform for human regenerative therapies. Due to the limited proliferation capacity of adult mammalian cardiomyocytes, the human heart has negligible regenerative capacity after injury. Here the authors show that a Hedgehog-Gli1-Mycn signaling cascade regulates cardiomyocyte proliferation and cardiac regeneration from amphibians to mammals. |
| Databáze: | OpenAIRE |
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