title: Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers.
abstract: Satellite cells, which are skeletal muscle stem cells, divide to provide new myonuclei to growing muscle fibers during postnatal development, and then are maintained in an undifferentiated quiescent state in adult skeletal muscle. This state is considered to be essential for the maintenance of satellite cells, but their molecular regulation is unknown. We show that Hesr1 (Hey1) and Hesr3 (Heyl) (which are known Notch target genes) are expressed simultaneously in skeletal muscle only in satellite cells. In Hesr1 and Hesr3 single-knockout mice, no obvious abnormalities of satellite cells or muscle regenerative potentials are observed. However, the generation of undifferentiated quiescent satellite cells is impaired during postnatal development in Hesr1/3 double-knockout mice. As a result, myogenic (MyoD and myogenin) and proliferative (Ki67) proteins are expressed in adult satellite cells. Consistent with the in vivo results, Hesr1/3-null myoblasts generate very few Pax7(+) MyoD(-) undifferentiated cells in vitro. Furthermore, the satellite cell number gradually decreases in Hesr1/3 double-knockout mice even after it has stabilized in control mice, and an age-dependent regeneration defect is observed. In vivo results suggest that premature differentiation, but not cell death, is the reason for the reduced number of satellite cells in Hesr1/3 double-knockout mice. These results indicate that Hesr1 and Hesr3 are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis.
authors: Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. fukada@phs.osaka-u.ac.jp
authors: So-ichiro
authors: S
authors: Fukada
authors: Masahiko
authors: M
authors: Yamaguchi
authors: Hiroki
authors: H
authors: Kokubo
authors: Ryo
authors: R
authors: Ogawa
authors: Akiyoshi
authors: A
authors: Uezumi
authors: Tomohiro
authors: T
authors: Yoneda
authors: Miroslav M
authors: MM
authors: Matev
authors: Norio
authors: N
authors: Motohashi
authors: Takahito
authors: T
authors: Ito
authors: Anna
authors: A
authors: Zolkiewska
authors: Randy L
authors: RL
authors: Johnson
authors: Yumiko
authors: Y
authors: Saga
authors: Yuko
authors: Y
authors: Miyagoe-Suzuki
authors: Kazutake
authors: K
authors: Tsujikawa
authors: Shin'ichi
authors: S
authors: Takeda
authors: Hiroshi
authors: H
authors: Yamamoto
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009929:Organ Size; D010641:Phenotype; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D018797:Cell Cycle Proteins; C120420:Hey1 protein, mouse; C402588:Heyl protein, mouse