Atsushi Asakura, PhD

Associate Professor, Department of Neurology

Atsushi Asakura

Contact Info

Office Phone 612-624-7108

Fax 612-624-2436

Office Address:
Stem Cell Institute
McGuire Translational Research Faci
2001 6th St SE, Rm 4-220
Minneapolis, MN 55455

Mailing Address:
Stem Cell Institute
2001 6th St SE
Minneapolis, MN 55455

PhD, Institute of Medical Science and the National Institute of Neuroscience

Senior Post Doc, McMaster University and the Ottawa Health Research Institute


Dr. Atsushi Asakura is an Associate Professor of Neurology and a faculty member of the Stem Cell Institute in the University of Minnesota Medical School. He also belongs to Paul & Sheila Wellstone Muscular Dystrophy Center in the Medical School.


Dr. Asakura received his Ph.D. at the Institute of Medical Science at the University of Tokyo Graduate School and the National Institute of Neuroscience in Tokyo with Dr. Yo-ichi Nabeshima where he learned the molecular biology of skeletal muscle differentiation.

He trained at the post-doctoral level at the Fred Hutchinson Cancer Research Center in Seattle with Dr. Stephen J. Tapscott. His post-doctoral studies involved the transcription factors for skeletal muscle development during early embryogenesis.

He trained at the senior post-doctoral level at McMaster University in Hamilton and the Ottawa Health Research Institute in Ottawa with Dr. Michael A. Rudnicki where he started projects on skeletal muscle stem cells that contribute to muscle regeneration.


Research Summary/Interests

My laboratory’s goals include attempting to understand the molecular mechanisms controlling muscle satellite cell (muscle stem cell) self-renewal and differentiation, and to develop novel therapeutic methods for Duchenne Muscular Dystrophy (DMD). This also involves the stem cell niche associated with vasculature in normal and regenerating skeletal muscle. And, we have recently begun exploration of cell based therapy with induced Pluripotent Stem Cells (iPSCs) toward muscular dystrophy model animals and heart infarction models.

  • Genetically modified muscle stem cell therapy (Asakura et al., Proc. Natl. Acad. Sci. U S A, 2007, Hirai et al., J. Cell Biol., 2010):MyoD is a muscle-specific transcription factor that plays essential roles in muscle satellite cell differentiation and regeneration. We have demonstrated that myoblasts derived from MyoD-/- satellite cells engrafted with significantly higher efficacy compared to wild-type myoblasts after injection into regenerating muscle and infarcted heart. Importantly, in MyoD-/- myoblasts, anti-apoptotic genes such as Pax3, Bcl-2 and Bcl-xL were up-regulated through down-regulation of MyoD-target microRNAs, miR-1 and miR-206, while some pro-apoptotic genes such as GADD45 were down-regulated. Consistent with these expression profiles, MyoD-/- myoblasts were revealed to possess remarkable resistance to apoptosis and increased survival in vitro and in vivo. Therefore, MyoD is not only regulating terminal differentiation but also regulating apoptosis during myogenic differentiation. In addition, down-regulation of MyoD expression may be required for maintenance of self-renewing muscle stem cells. Our outcomes will reveal the developmental relationship between satellite cells as well as the molecular biology of cell differentiation, apoptosis and self-renewal processes. Furthermore, our data offer evidence for novel therapeutic stem cell transplantation, in which suppression of MyoD in myogenic progenitor cells would be beneficial to the therapy for DMD and ischemic heart diseases by providing a selective advantage for expansion of the stem cells. Proc. Natl. Acad. Sci. U S A, 2007
  • Myoblast-derived induced Pluripotent Stem Cells (iPSCs) (Watanabe et al., Stem Cells, 2011): Expression of the four transcription factors; Oct4, Sox2, cMyc and Klf4 has been shown to generate induced pluripotent stem cells (iPSCs) from many types of differentiated somatic cells. It remains unclear, however, whether committed skeletal muscle stem cells and progenitor cells have the potency to undergo reprogramming to develop iPSCs in line with previously reported cases. To test this, we have isolated satellite cells from adult mouse muscles. Upon being infected with retroviral vector expressing the four factors, these satellite cell-derived myoblasts gave rise to embryonic stem cell (ESC)-like colonies. These cells expressed ES specific genes and were competent to differentiate into all three germ layers and germ cells, indicating the successful generation of muscle-derived iPSCs. Therefore, it would be advantageous to utilize the skeletal muscle system as a well defined differentiation model to further elaborate on the effects of iPSC reprogramming in somatic cells. Our hypothesis is that myoblast-derived iPSCs may maintain epigenetic memory of myogenic status, which might contribute to the higher myogenic differentiation potential. Therefore, the use of myoblast-derived iPSCs will be a potential cell therapy for DMD.
  • Angiogenic therapy for muscular dystrophy (Verma et al., Hum. Mol. Genet., 2010):DMD is an X-linked recessive genetic disease affecting one in 3,500 children caused by mutations in the gene coding for the protein dystrophin, which results in progressive muscle degeneration and vascular deficiency. For an effective form of therapy of DMD, both the muscle and the vasculature need to be addressed. To reveal the developmental relationship between muscular dystrophy and vasculature, mdx mice, an animal model for DMD, were crossed withFlt-1 gene knockout mice to create a model with increased vasculature. Flt-1 is a decoy receptor for vascular endothelial growth factor (VEGF), and therefore both homozygous (Flt-1-/-) and heterozygous (Flt-1+/-) Flt-1 gene knockout mice display increased endothelial cell proliferation and vascular density during development. We show the mdx:Flt-1+/- mice display improved muscle histology, and an increase in muscle blood flow and force production, compared to themdx mice. Consequently, the mdx:utrophin-/-:Flt-1+/- mice display improved muscle histology and significantly higher survival rates compared to the mdx:utrophin-/- mice which show more severe muscle phenotypes than the mdx mice. Importantly, increased vascular niche in themdx:Flt-1+/- mice results in increased satellite cell number, which may be responsible for theimproved muscle phenotype seen in the these mice. These data suggest that increasing the vasculature in DMD may ameliorate the histological and functional phenotypes associated with this disease.