title: Self-renewal and differentiation of muscle satellite cells are regulated by the Fas-associated death domain.
abstract: Making the decision between self-renewal and differentiation of adult stem cells is critical for tissue repair and homeostasis. Here we show that the apoptotic adaptor Fas-associated death domain (FADD) regulates the fate decisions of muscle satellite cells (SCs). FADD phosphorylation was specifically induced in cycling SCs, which was high in metaphase and declined in later anaphase. Furthermore, phosphorylated FADD at Ser-191 accumulated in the uncommitted cycling SCs and was asymmetrically localized in the self-renewing daughter SCs. SCs containing a phosphoryl-mimicking mutation at Ser-191 of FADD (FADD-D) expressed higher levels of stem-like markers and reduced commitment-associated markers. Moreover, a phosphoryl-mimicking mutation at Ser-191 of FADD suppressed SC activation and differentiation, which promoted the cycling SCs into a reversible quiescent state. Therefore, these data indicate that FADD regulates the fate determination of cycling SCs.
authors.affiliation: From the State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing 210093, Jiangsu, China and.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Bingya
authors.initials: B
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Yao
authors.forename: Liangqiang
authors.initials: L
authors.lastname: He
authors.forename: Zexu
authors.initials: Z
authors.lastname: Liu
authors.forename: Pan
authors.initials: P
authors.lastname: Du
authors.forename: Kahina
authors.initials: K
authors.lastname: Hammache
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.forename: Huang
authors.initials: H
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Zichun
authors.initials: Z
authors.lastname: Hua
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D006614:Hindlimb; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D010766:Phosphorylation; D051880:Receptors, Notch / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D051880:Receptors, Notch
keywords: Cell Cycle; Differentiation; Muscle; Notch Pathway; Stem Cells