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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genome-wide; R/bioconductor Package; Sclerostin Antibody; Differential Gene; Image-analysis; Bone-formation; Sost Gene; R Package; In-vitro; Osteoblast
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 2444 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506700-001
Förderungen 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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