Notch ligands regulate the muscle stem-like state ex vivo but are not sufficient for retaining regenerative capacity
| Autor: | So-ichiro Fukada, Sumiaki Fukuda, Miki Nakamura, Shahragim Tajbakhsh, Hiroshi Sakai, Takahiko Sato, Akiyoshi Uezumi, Harumoto Yamada, Mitsuhiro Morita, Yu Taro Noguchi, Kunihiro Tsuchida |
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| Přispěvatelé: | Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Osaka University [Osaka], Fujita Health University, Kyoto University, So-ichiro F. and A.U. were supported by Japan Agency for Medical Research and Development. S.T. was funded by Institut Pasteur, Centre National pour la Recherche Scientific, the Agence Nationale de la Recherche (Laboratoire d’Excellence Revive, Investissement d’Avenir, ANR-10-LABX- 73) and the European Research Council (Advanced Research Grant 332893)., We like to thank Clémire Cimper for technical support and members of the SF group and ST labs for helpful discussions., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Kyoto University [Kyoto] |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MESH: Signal Transduction MESH: Muscle Cells Cell Transplantation medicine.medical_treatment [SDV]Life Sciences [q-bio] lcsh:Medicine MyoD Muscle Development Myoblasts Mice Cell Signaling Animal Cells Morphogenesis Medicine and Health Sciences Blood and Lymphatic System Procedures Myocyte MESH: Animals lcsh:Science Musculoskeletal System Cells Cultured Notch Signaling Multidisciplinary Receptors Notch Chemistry MESH: Real-Time Polymerase Chain Reaction Stem Cells Stem Cell Therapy Muscles MESH: Regeneration Intracellular Signaling Peptides and Proteins PAX7 Transcription Factor Cell Differentiation Stem-cell therapy Muscle Differentiation Immunohistochemistry Cell biology MESH: Muscle Development Intercellular Signaling Peptides and Proteins MESH: Membrane Proteins Stem cell Cellular Types Anatomy Muscle Regeneration MESH: Cells Cultured Signal Transduction Research Article MESH: Cell Differentiation JAG1 MESH: Jagged-1 Protein Notch signaling pathway Muscle Tissue Surgical and Invasive Medical Procedures MESH: Stem Cells [SDV.BC]Life Sciences [q-bio]/Cellular Biology Muscle disorder Real-Time Polymerase Chain Reaction 03 medical and health sciences MESH: Intracellular Signaling Peptides and Proteins medicine Animals Regeneration MESH: Myoblasts MESH: Intercellular Signaling Peptides and Proteins MESH: Mice MyoD Protein Clinical Genetics Muscle Cells Transplantation MESH: MyoD Protein lcsh:R Calcium-Binding Proteins Membrane Proteins Biology and Life Sciences MESH: Immunohistochemistry Cell Biology 030104 developmental biology MESH: PAX7 Transcription Factor Biological Tissue Skeletal Muscles lcsh:Q MESH: Receptors Notch Organism Development Ex vivo Jagged-1 Protein Developmental Biology Stem Cell Transplantation |
| Zdroj: | PLoS ONE PLoS ONE, 2017, 12 (5), pp.e0177516. ⟨10.1371/journal.pone.0177516⟩ PLoS ONE, Public Library of Science, 2017, 12 (5), pp.e0177516. ⟨10.1371/journal.pone.0177516⟩ PLoS ONE, Vol 12, Iss 5, p e0177516 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0177516⟩ |
| Popis: | International audience; Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency. Notch signaling promotes the expansion of Pax7+MyoDmouse muscle stem-like cells and inhibits differentiation even after passage in vitro. Treatment with Notch ligands induced the Notch target genes and generated PAX7+MYODstem- like cells from human myoblasts previously cultured on conventional culture plates. However, cells treated with Notch ligands exhibit a stem cell-like state in culture, yet their regenerative ability was less than that of freshly isolated cells in vivo and was comparable to that of the control. These unexpected findings suggest that artificial maintenance of Notch signaling alone is insufficient for improving regenerative capacity of mouse and human donor-muscle cells and suggest that combinatorial events are critical to achieve muscle stem cell and myoblast engraftment potential. |
| Databáze: | OpenAIRE |
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