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PMID: 7568232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 21 ·1995-10-10 ·Pages 9856-60

Hu E, Tontonoz P, Spiegelman BM

Abstract

Skeletal muscle and adipose tissue development often has a reciprocal relationship in vivo, particularly in myodystrophic states. We have investigated whether determined myoblasts with no inherent adipogenic potential can be induced to transdifferentiate into mature adipocytes by the ectopic expression of two adipogenic transcription factors, PPAR gamma and C/EBP alpha. When cultured under optimal conditions for muscle differentiation, murine G8 myoblasts expressing PPAR gamma and C/EBP alpha show markedly reduced levels of the myogenic basic helix-loop-helix proteins MyoD, myogenin, MRF4, and myf5 and are completely unable to differentiate into myotubes. Under conditions permissive for adipogenesis including a PPAR activator, these cells differentiate into mature adipocytes that express molecular markers characteristic of this lineage. Our results demonstrate that a developmental switch between these two related but highly specialized cell types can be controlled by the expression of key adipogenic transcription factors. These factors have an ability to inhibit myogenesis that is temporally and functionally separate from their ability to stimulate adipogenesis.

MeSH Terms
Adipocytes/cytology Adipose Tissue/cytology,growth & development Animals Biomarkers Blotting, Northern CCAAT-Enhancer-Binding Proteins Cell Differentiation Cells, Cultured DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation, Developmental Genetic Vectors Helix-Loop-Helix Motifs Mice Muscle Development Muscle, Skeletal/cytology,growth & development Myogenic Regulatory Factors/metabolism Nuclear Proteins/genetics,metabolism Receptors, Cytoplasmic and Nuclear/genetics,metabolism Recombinant Proteins/metabolism Stem Cells/metabolism Transcription Factors/genetics,metabolism
Chemicals
Biomarkers CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Myogenic Regulatory Factors Nuclear Proteins Receptors, Cytoplasmic and Nuclear Recombinant Proteins Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hu E
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Tontonoz P
Spiegelman B M
References (44)
44 references, click to expand
  1. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  2. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5434-8 PMID: 2748593
  3. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion.
    Cell. 1975 May;5(1):19-27 PMID: 165899
  4. Synapse formation between two clonal cell lines.
    Science. 1977 May 27;196(4293):995-8 PMID: 193191
  5. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine.
    Cell. 1979 Aug;17(4):771-9 PMID: 90553
  6. Pre-adipocyte determination either by insulin or by 5-azacytidine.
    Proc Natl Acad Sci U S A. 1982 Jan;79(2):480-4 PMID: 6176995
  7. 5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination.
    Cell. 1984 Oct;38(3):791-800 PMID: 6207933
  8. Plasticity of the differentiated state.
    Science. 1985 Nov 15;230(4727):758-66 PMID: 2414846
  9. Expression of human class II major histocompatibility complex antigens using retrovirus vectors.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2150-4 PMID: 3031667
  10. How fixed is the differentiated state? Lessons from heterokaryons.
    Trends Genet. 1989 Aug;5(8):268-72 PMID: 2686116
  11. Prader-Willi syndrome: current understanding of cause and diagnosis.
    Am J Med Genet. 1990 Mar;35(3):319-32 PMID: 2309779
  12. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins.
    Cell. 1990 Apr 6;61(1):49-59 PMID: 2156629
  13. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.
    Nucleic Acids Res. 1990 Jun 25;18(12):3587-96 PMID: 2194165
  14. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
    Nature. 1990 Oct 18;347(6294):645-50 PMID: 2129546
  15. Id: a negative regulator of helix-loop-helix DNA binding proteins. Control of terminal myogenic differentiation.
    Ann N Y Acad Sci. 1990;599:1-11 PMID: 2171390
  16. CCAAT-enhancer binding protein: a component of a differentiation switch.
    Science. 1991 Jan 18;251(4991):288-92 PMID: 1987644
  17. The myoD gene family: nodal point during specification of the muscle cell lineage.
    Science. 1991 Feb 15;251(4995):761-6 PMID: 1846704
  18. Cell culture models of differentiation.
    FASEB J. 1991 Mar 1;5(3):287-94 PMID: 2001788
  19. 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO.
    Nucleic Acids Res. 1991 Jul 25;19(14):3998 PMID: 1861990
  20. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.
    Genes Dev. 1991 Sep;5(9):1538-52 PMID: 1840554
  21. Making muscle in mammals.
    Trends Genet. 1992 Apr;8(4):144-8 PMID: 1321521
  22. Differentiation requires continuous active control.
    Annu Rev Biochem. 1992;61:1213-30 PMID: 1497309
  23. The molecular and biochemical basis of Duchenne muscular dystrophy.
    Trends Biochem Sci. 1992 Aug;17(8):289-92 PMID: 1412702
  24. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160-4 PMID: 8384714
  25. Cytogenetic and molecular studies in the Prader-Willi and Angelman syndromes: an overview.
    Am J Med Genet. 1993 Apr 1;46(1):2-6 PMID: 8388170
  26. Skeletal myogenesis: genetics and embryology to the fore.
    Curr Opin Genet Dev. 1993 Apr;3(2):265-74 PMID: 8389217
  27. Production of high-titer helper-free retroviruses by transient transfection.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6 PMID: 7690960
  28. The MyoD family and myogenesis: redundancy, networks, and thresholds.
    Cell. 1993 Dec 31;75(7):1241-4 PMID: 8269506
  29. MyoD or Myf-5 is required for the formation of skeletal muscle.
    Cell. 1993 Dec 31;75(7):1351-9 PMID: 8269513
  30. bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out.
    Genes Dev. 1994 Jan;8(1):1-8 PMID: 8288123
  31. Posttranscriptional regulation of Id1 activity in cardiac muscle. Alternative splicing of novel Id1 transcript permits homodimerization.
    J Biol Chem. 1994 Feb 18;269(7):5132-6 PMID: 8106493
  32. Transdifferentiation.
    Curr Opin Cell Biol. 1993 Dec;5(6):1023-8 PMID: 8129939
  33. Extracellular matrix alters epithelial differentiation.
    Curr Opin Cell Biol. 1993 Dec;5(6):1029-35 PMID: 8129940
  34. Plasticity in neural crest cell differentiation.
    Curr Opin Cell Biol. 1993 Dec;5(6):1036-43 PMID: 8129941
  35. Reversibility of the differentiated state in somatic cells.
    Curr Opin Cell Biol. 1993 Dec;5(6):1050-6 PMID: 8129943
  36. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9 PMID: 8041794
  37. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program.
    Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8757-61 PMID: 8090719
  38. Wiring diagrams: regulatory circuits and the control of skeletal myogenesis.
    Curr Opin Cell Biol. 1994 Jun;6(3):432-42 PMID: 7917336
  39. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
    Genes Dev. 1994 May 15;8(10):1224-34 PMID: 7926726
  40. Regulation of adipocyte development.
    Annu Rev Nutr. 1994;14:99-129 PMID: 7946535
  41. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells.
    Genes Dev. 1994 Jul 15;8(14):1654-63 PMID: 7958846
  42. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
    Cell. 1994 Dec 30;79(7):1147-56 PMID: 8001151
  43. PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene.
    Mol Cell Biol. 1995 Jan;15(1):351-7 PMID: 7799943
  44. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.
    Genes Dev. 1995 Jan 15;9(2):168-81 PMID: 7531665
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.21.9856
Published
1995-10-10
Pages
9856-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40901
Subset
IM
Grants
NIDDK NIH HHS · DK31405 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.21.9856 PMC Full Text View journal details
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