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

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...

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Autores principales: Youlten, Scott E., Kemp, John P., Logan, John G., Ghirardello, Elena J., Sergio, Claudio M., Dack, Michael R. G., Guilfoyle, Siobhan E., Leitch, Victoria D., Butterfield, Natalie C., Komla-Ebri, Davide, Chai, Ryan C., Corr, Alexander P., Smith, James T., Mohanty, Sindhu T., Morris, John A., McDonald, Michelle M., Quinn, Julian M. W., McGlade, Amelia R., Bartonicek, Nenad, Jansson, Matt, Hatzikotoulas, Konstantinos, Irving, Melita D., Beleza-Meireles, Ana, Rivadeneira, Fernando, Duncan, Emma, Richards, J. Brent, Adams, David J., Lelliott, Christopher J., Brink, Robert, Phan, Tri Giang, Eisman, John A., Evans, David M., Zeggini, Eleftheria, Baldock, Paul A., Bassett, J. H. Duncan, Williams, Graham R., Croucher, Peter I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100170/
https://www.ncbi.nlm.nih.gov/pubmed/33953184
http://dx.doi.org/10.1038/s41467-021-22517-1
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author Youlten, Scott E.
Kemp, John P.
Logan, John G.
Ghirardello, Elena J.
Sergio, Claudio M.
Dack, Michael R. G.
Guilfoyle, Siobhan E.
Leitch, Victoria D.
Butterfield, Natalie C.
Komla-Ebri, Davide
Chai, Ryan C.
Corr, Alexander P.
Smith, James T.
Mohanty, Sindhu T.
Morris, John A.
McDonald, Michelle M.
Quinn, Julian M. W.
McGlade, Amelia R.
Bartonicek, Nenad
Jansson, Matt
Hatzikotoulas, Konstantinos
Irving, Melita D.
Beleza-Meireles, Ana
Rivadeneira, Fernando
Duncan, Emma
Richards, J. Brent
Adams, David J.
Lelliott, Christopher J.
Brink, Robert
Phan, Tri Giang
Eisman, John A.
Evans, David M.
Zeggini, Eleftheria
Baldock, Paul A.
Bassett, J. H. Duncan
Williams, Graham R.
Croucher, Peter I.
author_facet Youlten, Scott E.
Kemp, John P.
Logan, John G.
Ghirardello, Elena J.
Sergio, Claudio M.
Dack, Michael R. G.
Guilfoyle, Siobhan E.
Leitch, Victoria D.
Butterfield, Natalie C.
Komla-Ebri, Davide
Chai, Ryan C.
Corr, Alexander P.
Smith, James T.
Mohanty, Sindhu T.
Morris, John A.
McDonald, Michelle M.
Quinn, Julian M. W.
McGlade, Amelia R.
Bartonicek, Nenad
Jansson, Matt
Hatzikotoulas, Konstantinos
Irving, Melita D.
Beleza-Meireles, Ana
Rivadeneira, Fernando
Duncan, Emma
Richards, J. Brent
Adams, David J.
Lelliott, Christopher J.
Brink, Robert
Phan, Tri Giang
Eisman, John A.
Evans, David M.
Zeggini, Eleftheria
Baldock, Paul A.
Bassett, J. H. Duncan
Williams, Graham R.
Croucher, Peter I.
author_sort Youlten, Scott E.
collection PubMed
description 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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spelling pubmed-81001702021-05-11 Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease Youlten, Scott E. Kemp, John P. Logan, John G. Ghirardello, Elena J. Sergio, Claudio M. Dack, Michael R. G. Guilfoyle, Siobhan E. Leitch, Victoria D. Butterfield, Natalie C. Komla-Ebri, Davide Chai, Ryan C. Corr, Alexander P. Smith, James T. Mohanty, Sindhu T. Morris, John A. McDonald, Michelle M. Quinn, Julian M. W. McGlade, Amelia R. Bartonicek, Nenad Jansson, Matt Hatzikotoulas, Konstantinos Irving, Melita D. Beleza-Meireles, Ana Rivadeneira, Fernando Duncan, Emma Richards, J. Brent Adams, David J. Lelliott, Christopher J. Brink, Robert Phan, Tri Giang Eisman, John A. Evans, David M. Zeggini, Eleftheria Baldock, Paul A. Bassett, J. H. Duncan Williams, Graham R. Croucher, Peter I. Nat Commun Article 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. Nature Publishing Group UK 2021-05-05 /pmc/articles/PMC8100170/ /pubmed/33953184 http://dx.doi.org/10.1038/s41467-021-22517-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Youlten, Scott E.
Kemp, John P.
Logan, John G.
Ghirardello, Elena J.
Sergio, Claudio M.
Dack, Michael R. G.
Guilfoyle, Siobhan E.
Leitch, Victoria D.
Butterfield, Natalie C.
Komla-Ebri, Davide
Chai, Ryan C.
Corr, Alexander P.
Smith, James T.
Mohanty, Sindhu T.
Morris, John A.
McDonald, Michelle M.
Quinn, Julian M. W.
McGlade, Amelia R.
Bartonicek, Nenad
Jansson, Matt
Hatzikotoulas, Konstantinos
Irving, Melita D.
Beleza-Meireles, Ana
Rivadeneira, Fernando
Duncan, Emma
Richards, J. Brent
Adams, David J.
Lelliott, Christopher J.
Brink, Robert
Phan, Tri Giang
Eisman, John A.
Evans, David M.
Zeggini, Eleftheria
Baldock, Paul A.
Bassett, J. H. Duncan
Williams, Graham R.
Croucher, Peter I.
Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
title Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
title_full Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
title_fullStr Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
title_full_unstemmed Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
title_short Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
title_sort osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100170/
https://www.ncbi.nlm.nih.gov/pubmed/33953184
http://dx.doi.org/10.1038/s41467-021-22517-1
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