Systems genetics analysis of mouse chondrocyte differentiation.
One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development.
Department of Oral Biology, School of Dentistry, UCLA, Los Angeles, CA 90095, USA. jaijam1220@gmail.com
Jaijam
J
Suwanwela
Charles R
CR
Farber
Bau-Lin
BL
Haung
Buer
B
Song
Calvin
C
Pan
Karen M
KM
Lyons
Aldons J
AJ
Lusis
D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D000067879:CELF1 Protein; D002356:Cartilage / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D002875:Chromosomes / Q000235:genetics; D003094:Collagen / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D005269:Femur / Q000033:anatomy & histology / Q000737:chemistry; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000502:physiology*; D023281:Genomics / Q000379:methods*; D006025:Glycosaminoglycans / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D016013:Likelihood Functions; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000378:metabolism; D040641:Quantitative Trait Loci / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*
D000067879:CELF1 Protein; C502743:CELF1 protein, mouse; C493957:Cdkn1a protein, mouse; D018834:Chaperonin 60; D050659:Core Binding Factor Alpha 1 Subunit; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006025:Glycosaminoglycans; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; C557066:Hspd1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C493716:Runx2 protein, mouse; D003094:Collagen