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Youlten, S.E.* ; Kemp, J.P.* ; Logan, J.G.* ; Ghirardello, E.J.* ; Sergio, C.M.* ; Dack, M.R.G.* ; Guilfoyle, S.E.* ; Leitch, V.D.* ; Butterfield, N.C.* ; Komla-Ebri, D.* ; Chai, R.C.* ; Corr, A.P.* ; Smith, J.T.* ; Mohanty, S.T.* ; Morris, J.A.* ; McDonald, M.M.* ; Quinn, J.M.W.* ; McGlade, A.R.* ; Bartonicek, N.* ; Jansson, M.* ; Hatzikotoulas, K. ; Irving, M.D.* ; Beleza-Meireles, A.* ; Rivadeneira, F.* ; Duncan, E.* ; Richards, J.B.* ; Adams, D.J.* ; Lelliott, C.J.* ; Brink, R.* ; Phan, T.G.* ; Eisman, J.A.* ; Evans, D.M* ; Zeggini, E. ; Baldock, P.A.* ; Bassett, J.H.D.* ; Williams, G.R.* ; Croucher, P.I.*

Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

Nat. Commun. 12:2444 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
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Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 × 10-22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10-13) and osteoarthritis (P = 1.6 × 10-7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide; R/bioconductor Package; Sclerostin Antibody; Differential Gene; Image-analysis; Bone-formation; Sost Gene; R Package; In-vitro; Osteoblast
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 2444 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506700-001
Grants Department of Health
Medical Research Council
Cancer Research UK
CIHR
DOI 10.1038/s41467-021-22517-1
WOS ID WOS:000656476300001
Scopus ID 85105379914
PubMed ID 33953184
Erfassungsdatum 2021-06-14
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