TY - JOUR
T1 - Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
AU - Youlten, Scott E.
AU - Kemp, John P.
AU - Logan, John G.
AU - Ghirardello, Elena J.
AU - Sergio, Claudio M.
AU - Dack, Michael R.G.
AU - Guilfoyle, Siobhan E.
AU - Leitch, Victoria D.
AU - Butterfield, Natalie C.
AU - Komla-Ebri, Davide
AU - Chai, Ryan C.
AU - Corr, Alexander P.
AU - Smith, James T.
AU - Mohanty, Sindhu T.
AU - Morris, John A.
AU - McDonald, Michelle M.
AU - Quinn, Julian M.W.
AU - McGlade, Amelia R.
AU - Bartonicek, Nenad
AU - Jansson, Matt
AU - Hatzikotoulas, Konstantinos
AU - Irving, Melita D.
AU - Beleza-Meireles, Ana
AU - Rivadeneira, Fernando
AU - Duncan, Emma
AU - Richards, J. Brent
AU - Adams, David J.
AU - Lelliott, Christopher J.
AU - Brink, Robert
AU - Phan, Tri Giang
AU - Eisman, John A.
AU - Evans, David M.
AU - Zeggini, Eleftheria
AU - Baldock, Paul A.
AU - Bassett, J. H.Duncan
AU - Williams, Graham R.
AU - Croucher, Peter I.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85105379914
U2 - 10.1038/s41467-021-22517-1
DO - 10.1038/s41467-021-22517-1
M3 - Article
C2 - 33953184
AN - SCOPUS:85105379914
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2444
ER -