Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues

Abstract

Brown adipose tissues (BAT) are derived from a myogenic factor 5 (Myf5)-expressing cell lineage and white adipose tissues (WAT) predominantly arise from non-Myf5 lineages, although a subpopulation of adipocytes in some WAT depots can be derived from the Myf5 lineage. However, the functional implication of the Myf5- and non-Myf5-lineage cells in WAT is unclear. We found that the Myf5-lineage constitution in subcutaneous WAT depots is negatively correlated to the expression of classical BAT and newly defined beige/brite adipocyte-specific genes. Consistently, fluorescent-activated cell sorting (FACS)-purified Myf5-lineage adipo-progenitors give rise to adipocytes expressing lower levels of BAT-specific Ucp1, Prdm16, Cidea, and Ppargc1a genes and beige adipocyte-specific CD137, Tmem26, and Tbx1 genes compared with the non-Myf5-lineage adipocytes from the same depots. Ablation of the Myf5-lineage progenitors in WAT stromal vascular cell (SVC) cultures leads to increased expression of BAT and beige cell signature genes. Strikingly, the Myf5-lineage cells in WAT are heterogeneous and contain distinct adipogenic [stem cell antigen 1(Sca1)-positive] and myogenic (Sca1-negative) progenitors. The latter differentiate robustly into myofibers in vitro and in vivo, and they restore dystrophin expression after transplantation into mdx mouse, a model for Duchenne muscular dystrophy. These results demonstrate the heterogeneity and functional differences of the Myf5- and non-Myf5-lineage cells in the white adipose tissue. Brown adipose tissues (BAT) are derived from a myogenic factor 5 (Myf5)-expressing cell lineage and white adipose tissues (WAT) predominantly arise from non-Myf5 lineages, although a subpopulation of adipocytes in some WAT depots can be derived from the Myf5 lineage. However, the functional implication of the Myf5- and non-Myf5-lineage cells in WAT is unclear. We found that the Myf5-lineage constitution in subcutaneous WAT depots is negatively correlated to the expression of classical BAT and newly defined beige/brite adipocyte-specific genes. Consistently, fluorescent-activated cell sorting (FACS)-purified Myf5-lineage adipo-progenitors give rise to adipocytes expressing lower levels of BAT-specific Ucp1, Prdm16, Cidea, and Ppargc1a genes and beige adipocyte-specific CD137, Tmem26, and Tbx1 genes compared with the non-Myf5-lineage adipocytes from the same depots. Ablation of the Myf5-lineage progenitors in WAT stromal vascular cell (SVC) cultures leads to increased expression of BAT and beige cell signature genes. Strikingly, the Myf5-lineage cells in WAT are heterogeneous and contain distinct adipogenic [stem cell antigen 1(Sca1)-positive] and myogenic (Sca1-negative) progenitors. The latter differentiate robustly into myofibers in vitro and in vivo, and they restore dystrophin expression after transplantation into mdx mouse, a model for Duchenne muscular dystrophy. These results demonstrate the heterogeneity and functional differences of the Myf5- and non-Myf5-lineage cells in the white adipose tissue. Adipose tissues play important roles in energy metabolism and life span of mammals. In mice, adipocytes can be broadly divided into white adipocytes, brown adipocytes, and beige (brite) adipocytes (1Walden T.B. Hansen I.R. Timmons J.A. Cannon B. Nedergaard J. Recruited vs. nonrecruited molecular signatures of brown, “brite,” and white adipose tissues.Am. J. Physiol. Endocrinol. Metab. 2012; 302: E19-E31Crossref PubMed Scopus (418) Google Scholar, 2Wu J. Cohen P. Spiegelman B.M. Adaptive thermogenesis in adipocytes: is beige the new brown?.Genes Dev. 2013; 27: 234-250Crossref PubMed Scopus (628) Google Scholar). A white adipocyte contains a single, large lipid droplet that stores triglycerides as chemical energy; by contrast, a brown adipocyte contains multiple small lipid droplets and numerous mitochondria that metabolize triglycerides through β-oxidation and oxidative respiration to generate heat to defend against hypothermia and obesity (3Cannon B. Nedergaard J. Brown adipose tissue: function and physiological significance.Physiol. Rev. 2004; 84: 277-359Crossref PubMed Scopus (4525) Google Scholar). The mitochondrial inner membranes of brown adipocytes uniquely express the uncoupling protein 1 (UCP1) that dissipates the proton gradient produced by the electron transfer chain, thus generating heat instead of ATP (3Cannon B. Nedergaard J. Brown adipose tissue: function and physiological significance.Physiol. Rev. 2004; 84: 277-359Crossref PubMed Scopus (4525) Google Scholar). A beige adipocyte is an adaptive thermogenic adipocyte found within white adipose tissues (WAT) induced by cold exposure (4Fisher F.M. Kleiner S. Douris N. Fox E.C. Mepani R.J. Verdeguer F. Wu J. Kharitonenkov A. Flier J.S. Maratos-Flier E. et al.FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis.Genes Dev. 2012; 26: 271-281Crossref PubMed Scopus (1101) Google Scholar, 5Smorlesi A. Frontini A. Giordano A. Cinti S. The adipose organ: white-brown adipocyte plasticity and metabolic inflammation.Obes. Rev. 2012; 13 (Suppl. 2): 83-96Crossref PubMed Scopus (125) Google Scholar) and hormonal stimulation (6Bostrom P. Wu J. Jedrychowski M.P. Korde A. Ye L. Lo J.C. Rasbach K.A. Bostrom E.A. Choi J.H. Long J.Z. et al.A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis.Nature. 2012; 481: 463-468Crossref PubMed Scopus (3082) Google Scholar, 7Ohno H. Shinoda K. Spiegelman B.M. Kajimura S. PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein.Cell Metab. 2012; 15: 395-404Abstract Full Text Full Text PDF PubMed Scopus (563) Google Scholar). A number of key gene regulatory factors have been shown to induce browning of white adipocytes (8Seale P. Conroe H.M. Estall J. Kajimura S. Frontini A. Ishibashi J. Cohen P. Cinti S. Spiegelman B.M. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice.J. Clin. Invest. 2011; 121: 96-105Crossref PubMed Scopus (914) Google Scholar, 9Shan T. Liang X. Bi P. Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1alpha-Fndc5 pathway in muscle.FASEB J. 2013; 27: 1981-1989Crossref PubMed Scopus (240) Google Scholar, 10Qiang L. Wang L. Kon N. Zhao W. Lee S. Zhang Y. Rosenbaum M. Zhao Y. Gu W. Farmer S.R. et al.Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma.Cell. 2012; 150: 620-632Abstract Full Text Full Text PDF PubMed Scopus (563) Google Scholar–11Tseng Y.H. Kokkotou E. Schulz T.J. Huang T.L. Winnay J.N. Taniguchi C.M. Tran T.T. Suzuki R. Espinoza D.O. Yamamoto Y. et al.New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.Nature. 2008; 454: 1000-1004Crossref PubMed Scopus (847) Google Scholar). Like the brown adipocytes, beige adipocytes express UCP1 and respond to cyclic AMP stimulation. However, beige adipocytes are distinct from the white and brown adipocytes, and they can be identified by their unique expression of several markers, including CD137, transmembrane protein 26 (Tmem26), and T-box 1 (Tbx1) (12Wu J. Bostrom P. Sparks L.M. Ye L. Choi J.H. Giang A.H. Khandekar M. Virtanen K.A. Nuutila P. Schaart G. et al.Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.Cell. 2012; 150: 366-376Abstract Full Text Full Text PDF PubMed Scopus (2313) Google Scholar). The myogenic factor 5 (Myf5) is a gene expressed during embryonic myogenesis and one of the core transcriptional factors involved in muscle development (13Braun T. Buschhausendenker G. Bober E. Tannich E. Arnold H.H. A novel human-muscle factor related to but distinct from Myod1 induces myogenic conversion in 10T1/2 fibroblasts.EMBO J. 1989; 8: 701-709Crossref PubMed Scopus (658) Google Scholar, 14Ott M.O. Bober E. Lyons G. Arnold H. Buckingham M. Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal-muscle in the mouse embryo.Development. 1991; 111: 1097-1107Crossref PubMed Google Scholar). Genetic-lineage tracing indicates that the classical brown adipocytes and skeletal muscle are derived from Myf5-expressing progenitors, while the white and beige adipocytes are predominately from the non-Myf5-lineage progenitors P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google Scholar). However, a by and that a of white adipocytes is derived from the Myf5-lineage progenitors J. C.M. Sparks Y. H. in the Myf5 lineage fat and of white adipocytes that arise from Myf5 Metab. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar). The of Myf5-lineage cells to WAT to WAT depots J. C.M. Sparks Y. H. in the Myf5 lineage fat and of white adipocytes that arise from Myf5 Metab. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar). of Myf5 during lineage cells to a of white adipocytes in depots W. Y. X. Kuang S. adipose is derived from a lineage and for of skeletal 2012; PubMed Scopus Google Scholar). to the Myf5-lineage of brown adipocytes, is to that the Myf5-lineage progenitors are to give rise to the adaptive beige However, the functional implication of Myf5-lineage and non-Myf5-lineage adipocytes been been that WAT contains an and of cells with multiple Adipose tissue the WAT Endocrinol. Metab. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar, F. an the to 2012; PubMed Scopus (125) Google H. M. cells as a novel for 2012; PubMed Scopus Google Scholar). from the stromal vascular of WAT can differentiate into adipocytes, and cells H. M. cells as a novel for 2012; PubMed Scopus Google Scholar, for and PubMed Scopus Google Scholar, W. J. fat with the of adipose Full Text Full Text PDF PubMed Scopus Google Scholar, cells in 2011; PubMed Scopus Google H. tissue and 2012; PubMed Scopus Google Scholar). been shown that adipose progenitors have myogenic in vitro and in G. A. S. A. A. F. of PubMed Scopus Google Scholar, J.H. cells myogenic and function in PubMed Scopus Google Scholar). that the myogenic progenitors are in the of cells in WAT T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). A is the of WAT cells results from a cell from of progenitors. the latter is are the unique for subpopulation of In cell cell sorting and cell transplantation to demonstrate the and function of the Myf5-lineage and non-Myf5-lineage progenitors in depots of subcutaneous adipose tissue a tissue that plasticity in We that the Myf5-lineage cells contain of adipogenic and myogenic progenitors that can be We found that the Myf5-lineage adipocytes expressed lower levels of brown and beige adipocyte the non-Myf5-lineage adipocytes within the same depots. We the Myf5-lineage myogenic progenitors of the cells and found that the Myf5-lineage progenitors are the that the myogenic The Myf5-lineage myogenic progenitors are of dystrophin expression in mdx and after transplantation into These results new into the roles of Myf5-lineage cells in white adipose tissue and that Myf5-lineage cells in the BAT and WAT are in with and in the with to and from and mdx The by the The white adipose cells by W. Y. X. Kuang S. adipose is derived from a lineage and for of skeletal 2012; PubMed Scopus Google Scholar, T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). the subcutaneous WAT WAT and WAT and into The WAT in for The with and through to tissues and of for 5 to the cells in the and the adipocytes in the The cells from the WAT and in with for by with adipogenic the cells induced with and for and in and for adipocytes myogenic the cells induced with for Myf5-lineage cells in the cells from WAT and BAT of the with for the of cell adipogenic myogenic the and cells induced to differentiate they cells type and W. Y. Bi P. X. X. Kuang S. cell and the of 2012; PubMed Scopus Google Scholar). the skeletal the from the and The with and the cells through and for 5 The cells and in with factor and with The with to during for transplantation cells cells from tissues of as The protein and cells Myf5-lineage and non-Myf5-lineage cells with lineage and with and cell antigen 1 with as T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). from cells and through cells from as for the and of cells expression and cells and to their adipogenic and myogenic and as W. Y. X. Kuang S. adipose is derived from a lineage and for of skeletal 2012; PubMed Scopus Google Scholar, T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). from cells to the with to The and of by a and of of and 5 of and in a with and are from (12Wu J. Bostrom P. Sparks L.M. Ye L. Choi J.H. Giang A.H. Khandekar M. Virtanen K.A. Nuutila P. Schaart G. et al.Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.Cell. 2012; 150: 366-376Abstract Full Text Full Text PDF PubMed Scopus (2313) Google Scholar, W. Y. X. Kuang S. adipose is derived from a lineage and for of skeletal 2012; PubMed Scopus Google Scholar, T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). of as and to the expression levels of genes. The protein and as T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). protein from cells and by to a and with the The and from and from the The and with a as T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). tissue with and the cells with and in for the with in with the with and for a The cells and the cells from of with 1 and into of to mdx 5 the and the and for expression a and The from the skeletal the into as the are as by as the of Myf5-lineage cells in and M. P. Early regulates expression and PubMed Google Scholar, L. Gu H. et al.A and and for the mouse PubMed Scopus Google in Myf5-lineage cells by an with P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google the of cells in muscle and BAT that the Myf5 lineage to the of lineage tracing cells in the and but in the cells can be in depots of the and with adipocyte that the cells in adipose depots are adipocytes These results demonstrate that a subpopulation of adipocytes in WAT depots is derived from the Myf5-lineage progenitors. the Myf5 lineage rise to adipose progenitors in the cells and found cells in the cells that are and cells in the of and some of the cells are adipogenic progenitors, the expression of an for adipose cells K. of white adipocyte cells in 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, W. M. fat cells in the adipose 2008; PubMed Scopus Google Scholar). to for that and of cells in and for We induced the cells to adipogenic and and of adipocytes in the and that Myf5-lineage cells have the adipogenic in results that a subpopulation of WAT adipocytes and cells are derived from Myf5-lineage number of Myf5-lineage adipocytes negatively to BAT and beige genes expression in depots. of the and after and adipocyte of the and after of brown adipocyte Prdm16, Cidea, and and beige cell Tmem26, in the and that BAT adipocytes are derived from the Myf5 lineage P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google that Myf5-lineage adipocytes in WAT express levels of BAT and beige signature genes. the of Myf5-lineage adipocytes in WAT depots the expression of BAT signature including Ucp1, Prdm16, Cidea, and to found that the of adipocytes in the and correlated to the levels of the BAT genes the expression of beige adipocyte and Tbx1 correlated to the of adipocytes in the and The the of Myf5-lineage adipocytes and gene expression in WAT depots be to differences Myf5-lineage Myf5-lineage and non-Myf5-lineage adipocytes within the same WAT expressed levels of genes. We from the by and of cells We induced to adipogenic and the expression of in the cells adipogenic and the and cells adipogenic as is from their expression levels of and to the cells rise to numerous after adipogenic the cells to adipocytes with the rise to adipocytes expressing lower levels of BAT genes Ucp1, Prdm16, Cidea, and Ppargc1a compared with the adipocytes the adipocytes expressed lower levels of beige genes CD137, Tmem26, and Tbx1 compared with the adipocytes expression in Myf5-lineage and non-Myf5-lineage adipocytes derived from that the Myf5-lineage adipocytes are brown the non-Myf5-lineage adipocytes within the same WAT the mouse model W. Y. X. Kuang S. adipose is derived from a lineage and for of skeletal 2012; PubMed Scopus Google Scholar, T. M. S. A. A cell lineage after PubMed Scopus Google Scholar). In induces the expression of is expressed by and the Myf5-lineage cells to Myf5-lineage cells but the non-Myf5-lineage cells from with to the Myf5-lineage to and induced to adipogenic Ablation of Myf5-lineage cells the of and the expression of the adipocyte and but the levels of BAT Ucp1, Prdm16, Cidea, and The beige cell and Tbx1 increased after of Myf5-lineage cells the of Myf5-lineage and non-Myf5-lineage adipocytes and lineage demonstrate that Myf5-lineage adipocytes express lower levels of brown and beige adipocyte the non-Myf5-lineage cells have the to differentiate into multiple lineages, including and myogenic cells in 2011; PubMed Scopus Google Scholar). that the adipogenic and myogenic by a cell but in distinct cell We to the lineage of myogenic progenitors in WAT depots. We cells from the of and induced to myogenic of the that they have been predominantly derived from the Myf5-lineage the Myf5-lineage cells for the myogenic of WAT lineage cells from of with to the Myf5-lineage to and induced to myogenic Ablation of Myf5-lineage cells the of In the numerous after contrast, the The levels of myogenic markers, as and after that the protein levels of and to levels after results in cells after the Myf5-lineage These results that Myf5-lineage cells are for the myogenic of the WAT We results by and cells to the cells small after induced in the with a in the and in the Consistently, the expression levels of myogenic genes and in the in the results demonstrate that the myogenic of the WAT cells in the Myf5-lineage progenitors. the myogenic of Myf5-lineage cells in vivo, the cells from the of to muscle of after myofibers in the cells predominantly expressed and myogenic P. A. A. P. is for the of myogenic Full Text Full Text PDF PubMed Scopus Google Scholar, Y. cells a for 2004; PubMed Scopus Google Scholar). These results that the Myf5-lineage cells a of myogenic progenitors of into myofibers in the the cells into myofibers expressing in the muscle of predominantly myofibers contrast, from skeletal to the myofibers expressing but These results that Myf5-lineage myogenic cells are from the skeletal in gene demonstrate the of the myogenic progenitors, the cells into mdx that the dystrophin gene, thus a model for Duchenne muscular dystrophy. We cells into of mdx in the mice, while in the These results demonstrate that the cells a myogenic that can be to muscular In the and functional differences of Myf5-lineage and non-Myf5-lineage adipocytes in WAT depots. We that the Myf5-lineage adipocytes in WAT express lower levels of BAT and beige genes the non-Myf5-lineage In that the Myf5-lineage cells in WAT contain distinct of adipogenic and myogenic progenitors, and that the myogenic progenitors can be to restore muscle function in an model of muscular dystrophy. important in is lineage cell The of Myf5-lineage to results that the subcutaneous WAT depots and within WAT the is lineage tracing and and gene expression that the Myf5-lineage and non-Myf5-lineage WAT adipocytes have distinct and the that the Myf5-lineage WAT adipocytes are brown the non-Myf5-lineage WAT adipocytes is with the that the classical BAT adipocytes are derived from the Myf5 lineage and the WAT is predominantly from the non-Myf5 lineage P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google Scholar). the Myf5-lineage adipocytes in the and distinct BAT and WAT to have gene expression and that in tissues can the of a precursor cell the Myf5-lineage adipocytes in BAT and WAT have from distinct of Myf5-expressing progenitors that are and In as Myf5 is expressed by several and cell during development P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google Scholar, T. Arnold H.H. R. of the muscle regulatory gene results in development and Full Text PDF PubMed Scopus Google Scholar, M. G. P. cell lineages, and in mouse skeletal 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, H. J.A. M. R. Y. F. et of an cell from distinct PubMed Scopus Google Scholar, S. Buckingham of the myogenic conversion factor in the 121: PubMed Google K. F. and of cells in Full Text Full Text PDF PubMed Scopus Google is that the Myf5-lineage cells in BAT and WAT are from embryonic the that contains a into the expressed gene L. Gu H. et al.A and and for the mouse PubMed Scopus Google found that Myf5-lineage cells to the skeletal and but to The of Myf5-lineage adipocytes in subcutaneous and WAT is with the by and J. C.M. Sparks Y. H. in the Myf5 lineage fat and of white adipocytes that arise from Myf5 Metab. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar). results that lineage cell function within the same tissue but that cells derived from the same lineage have distinct function in brown adipocytes are derived from the lineage P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google that Myf5-lineage adipocytes in WAT the adaptive beige adipocytes that physiological function and gene expression with However, that the Myf5-lineage adipocytes in WAT express lower levels of BAT and beige adipocyte genes. We through multiple of the of Myf5-lineage adipocytes in the in is correlated to the expression levels of adipocyte genes. Myf5-lineage and non-Myf5-lineage adipocytes by from the same WAT expressed levels of with expression levels in the non-Myf5-lineage of the Myf5-lineage adipocytes in expression of genes. results are in with the by et that the adaptive beige adipocytes in the subcutaneous WAT are derived from non-Myf5 lineage P. B. Kajimura S. S. Kuang A. S. Conroe H.M. H. et a brown muscle 2008; 454: PubMed Scopus Google Scholar). a shown that and in WAT respond to stimulation J. C.M. Sparks Y. H. in the Myf5 lineage fat and of white adipocytes that arise from Myf5 Metab. 2012; Full Text Full Text PDF PubMed Scopus Google results that the Myf5-lineage WAT adipocytes are as they express lower levels of BAT and beige adipocyte-specific genes. that Myf5-lineage cells to beige adipocytes browning of We identified of Myf5-lineage progenitors in the adipogenic and myogenic progenitors. results are with as a for adipose cells and a for muscle cells K. of white adipocyte cells in 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, W. M. fat cells in the adipose 2008; PubMed Scopus Google Scholar, J. F. S. A. T. Buckingham M. of cells for skeletal muscle PubMed Scopus Google Scholar, of mouse myogenic functional heterogeneity of cells within and skeletal 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). The myogenic of Myf5-lineage cells in WAT is that Myf5-lineage give rise to muscle tissues K. F. and of cells in Full Text Full Text PDF PubMed Scopus Google Scholar). that the myogenic of adipose progenitors in the Myf5-lineage as of found in WAT cultures from the Myf5 lineage. In of the Myf5-lineage cells the myogenic of WAT The in vitro and in myogenic of cells been G. A. S. A. A. F. of PubMed Scopus Google Scholar, J.H. cells myogenic and function in PubMed Scopus Google Scholar). However, been is the of the in a of progenitors. results that the subpopulation adipogenic and subpopulation myogenic the that adipose cells of of cells with and lineage been shown that myogenic cells can be derived from adipose the myogenic progenitors are to skeletal is unclear. We have identified several but differences and skeletal myogenic The myogenic cells express skeletal and P. A. A. P. is for the of myogenic Full Text Full Text PDF PubMed Scopus Google Scholar, Y. cells a for 2004; PubMed Scopus Google Scholar). Like the skeletal the myogenic cells can differentiate into in vitro and in vivo, and they can restore dystrophin expression in mdx However, the myogenic cells into the skeletal from the into The of progenitors an in been that myofibers are to as muscular and L. H.M. are in Duchenne muscular Full Text PDF PubMed Scopus Google Scholar, P. L. G. of A expression in skeletal muscle and in mdx PubMed Scopus Google J. G. muscular 2012; PubMed Scopus Google Scholar). In myofibers express levels of the mitochondrial genes and they are to and metabolic S. R. mitochondrial in the of with type J. 2004; PubMed Scopus Google Scholar, S. G. in skeletal muscle in an 2013; PubMed Scopus Google Scholar, J. Wu H. Zhang Wu P. E. et drives the of muscle PubMed Scopus Google Zhang J. H. of muscle type and by 2004; PubMed Scopus Google Scholar). of markers, is with the myogenic of cells derived from bone and embryonic E. Y. E.A. L.M. expression in the mdx mouse by cell PubMed Scopus Google Scholar, M. L. B. A. A. M. R. et a cell that from the and into PubMed Google Scholar, A. P. induces the myogenic of cells during muscle Full Text Full Text PDF PubMed Scopus Google Y. M. M. F. M. G. R. L. M. K. et cells restore dystrophin expression and function in skeletal Clin. Invest. 2004; PubMed Scopus Google Scholar). In expression of the of cells in skeletal muscle L. S. A. Buckingham of and Myf5 the of skeletal muscle PubMed Scopus Google Scholar). However, results from the cells that the cells predominantly with myogenic Strikingly, the cells that the myogenic progenitors in WAT cells are for with have shown that the to skeletal in vitro in the cells G. A. S. A. A. F. of PubMed Scopus Google Scholar). have shown that cells with progenitors that rise to myofibers in cells are for progenitors that give rise to in 2008; PubMed Scopus Google Scholar). demonstrate that the myogenic progenitors in WAT cells from the cells T. W. Kuang S. protein expression a of adipocyte progenitors in white and brown adipose J. 2013; 27: PubMed Scopus Google Scholar). results that the Myf5-lineage cells are the myogenic progenitors in WAT and that cells are distinct from the myogenic cells derived from bone tissues that have been to express In demonstrate in that Myf5-lineage progenitors in subcutaneous WAT give rise to adipogenic and myogenic In the Myf5-lineage adipocytes express lower levels of BAT and beige cell the non-Myf5-lineage the Myf5-lineage myogenic progenitors in WAT can differentiate into myofibers in vitro and in vivo, but they are distinct from the myogenic progenitors from skeletal in These results novel into the adipogenic and myogenic of Myf5-lineage cells in be for metabolic and muscle The Wu for and mouse with subcutaneous WAT brown adipose tissue factor cell a defined embryonic WAT fluorescent-activated cell sorting WAT myogenic factor 5 protein cell antigen 1 subcutaneous adipose tissue T-box 1 transmembrane protein 26 uncoupling protein 1 white adipose tissue