Biomaterial Database

Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells. 2012

Barbara Gayraud-Morel, and Fabrice Chrétien, and Aurélie Jory, and Ramkumar Sambasivan, and Elisa Negroni, and Patricia Flamant, and Guillaume Soubigou, and Jean-Yves Coppée, and James Di Santo, and Ana Cumano, and Vincent Mouly, and Shahragim Tajbakhsh

Stem Cells and Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578, Paris, France.

Skeletal muscle stem cell fate in adult mice is regulated by crucial transcription factors, including the determination genes Myf5 and Myod. The precise role of Myf5 in regulating quiescent muscle stem cells has remained elusive. Here we show that most, but not all, quiescent satellite cells express Myf5 protein, but at varying levels, and that resident Myf5 heterozygous muscle stem cells are more primed for myogenic commitment compared with wild-type satellite cells. Paradoxically however, heterotypic transplantation of Myf5 heterozygous cells into regenerating muscles results in higher self-renewal capacity compared with wild-type stem cells, whereas myofibre regenerative capacity is not altered. By contrast, Pax7 haploinsufficiency does not show major modifications by transcriptome analysis. These observations provide a mechanism linking Myf5 levels to muscle stem cell heterogeneity and fate by exposing two distinct and opposing phenotypes associated with Myf5 haploinsufficiency. These findings have important implications for how stem cell fates can be modulated by crucial transcription factors while generating a pool of responsive heterogeneous cells.

UI	MeSH Term	Description	Entries
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051763	PAX7 Transcription Factor	A paired box transcription factor that is involved in EMBRYONIC DEVELOPMENT of the CENTRAL NERVOUS SYSTEM and SKELETAL MUSCLE.	Paired Box Protein Pax-7,Paired Box Transcription Factor 7,Transcription Factor PAX7,Factor PAX7, Transcription,PAX7, Transcription Factor,Paired Box Protein Pax 7,Transcription Factor, PAX7
D051787	Myogenic Regulatory Factor 5	A SKELETAL MUSCLE-specific transcription factor that contains a basic HELIX-LOOP-HELIX MOTIF. It plays an essential role in MUSCLE DEVELOPMENT.	Myf5 Transcription Factor,Myogenic Factor 5,Transcription Factor, Myf5
D053687	Adult Stem Cells	Tissue-specific stem cells (also known as Somatic Stem Cells) that appear during fetal development and remain in the body throughout life. The key functions of adult stem cells are to maintain and repair the specific tissues where they reside (e.g. skin or blood).	Adult Somatic Stem Cells,Somatic Adult Stem Cells,Somatic Stem Cells,Adult Stem Cell,Somatic Stem Cell,Stem Cell, Somatic,Stem Cells, Adult,Stem Cells, Somatic
D057895	Haploinsufficiency	A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.	Haploinsufficiencies
D018482	Muscle, Skeletal	A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.	Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles
D019070	Cell Lineage	The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.	Cell Lineages,Lineage, Cell,Lineages, Cell
D032448	Myoblasts, Skeletal	Precursor cells destined to differentiate into skeletal myocytes (MYOCYTES, SKELETAL).	Skeletal Myoblasts,Myoblast, Skeletal,Skeletal Myoblast