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5 results on '"Guilfoyle, SE"'

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

Author

Youlten, SE, Kemp, JP, Logan, JG, Ghirardello, EJ, Sergio, CM, Dack, MRG, Guilfoyle, SE, Leitch, VD, Butterfield, NC, Komla-Ebri, D, Chai, RC, Corr, AP, Smith, JT, Mohanty, ST, Morris, JA, McDonald, MM, Quinn, JMW, McGlade, AR, Bartonicek, N, Jansson, M, Hatzikotoulas, K, Irving, MD, Beleza-Meireles, A, Rivadeneira, F, Duncan, E, Richards, JB, Adams, DJ, Lelliott, CJ, Brink, R, Phan, TG, Eisman, JA, Evans, DM, Zeggini, E, Baldock, PA, Bassett, JHD, Williams, GR, Croucher, PI, Youlten, SE, Kemp, JP, Logan, JG, Ghirardello, EJ, Sergio, CM, Dack, MRG, Guilfoyle, SE, Leitch, VD, Butterfield, NC, Komla-Ebri, D, Chai, RC, Corr, AP, Smith, JT, Mohanty, ST, Morris, JA, McDonald, MM, Quinn, JMW, McGlade, AR, Bartonicek, N, Jansson, M, Hatzikotoulas, K, Irving, MD, Beleza-Meireles, A, Rivadeneira, F, Duncan, E, Richards, JB, Adams, DJ, Lelliott, CJ, Brink, R, Phan, TG, Eisman, JA, Evans, DM, Zeggini, E, Baldock, PA, Bassett, JHD, Williams, GR, and Croucher, PI

Abstract

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.

Published
2021

2. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

Author

McDonald, MM, Khoo, WH, Ng, PY, Xiao, Y, Zamerli, J, Thatcher, P, Kyaw, W, Pathmanandavel, K, Grootveld, AK, Moran, I, Butt, D, Nguyen, A, Warren, S, Biro, M, Butterfield, NC, Guilfoyle, SE, Komla-Ebri, D, Dack, MRG, Dewhurst, HF, Logan, JG, Li, Y, Mohanty, ST, Byrne, N, Terry, RL, Simic, MK, Chai, R, Quinn, JMW, Youlten, SE, Pettitt, JA, Abi-Hanna, D, Jain, R, Weninger, W, Lundberg, M, Sun, S, Ebetino, FH, Timpson, P, Lee, WM, Baldock, PA, Rogers, MJ, Brink, R, Williams, GR, Bassett, JHD, Kemp, JP, Pavlos, NJ, Croucher, PI, Phan, TG, McDonald, MM, Khoo, WH, Ng, PY, Xiao, Y, Zamerli, J, Thatcher, P, Kyaw, W, Pathmanandavel, K, Grootveld, AK, Moran, I, Butt, D, Nguyen, A, Warren, S, Biro, M, Butterfield, NC, Guilfoyle, SE, Komla-Ebri, D, Dack, MRG, Dewhurst, HF, Logan, JG, Li, Y, Mohanty, ST, Byrne, N, Terry, RL, Simic, MK, Chai, R, Quinn, JMW, Youlten, SE, Pettitt, JA, Abi-Hanna, D, Jain, R, Weninger, W, Lundberg, M, Sun, S, Ebetino, FH, Timpson, P, Lee, WM, Baldock, PA, Rogers, MJ, Brink, R, Williams, GR, Bassett, JHD, Kemp, JP, Pavlos, NJ, Croucher, PI, and Phan, TG

Abstract

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases. Tracking osteoclasts during cycles of fission and fusion reveals a transcriptionally distinct “osteomorph” population that are fusion competent, motile, and capable of forming osteoclasts that resorb bone.

Published
2021

3. Extracellular vesicles in the retina - putative roles in physiology and disease.

Author

Kalargyrou AA, Guilfoyle SE, Smith AJ, Ali RR, and Pearson RA

Abstract

The retina encompasses a network of neurons, glia and epithelial and vascular endothelia cells, all coordinating visual function. Traditionally, molecular information exchange in this tissue was thought to be orchestrated by synapses and gap junctions. Recent findings have revealed that many cell types are able to package and share molecular information via extracellular vesicles (EVs) and the technological advancements in visualisation and tracking of these delicate nanostructures has shown that the role of EVs in cell communication is pleiotropic. EVs are released under physiological conditions by many cells but they are also released during various disease stages, potentially reflecting the health status of the cells in their cargo. Little is known about the physiological role of EV release in the retina. However, administration of exogenous EVs in vivo after injury suggest a neurotrophic role, whilst photoreceptor transplantation in early stages of retina degeneration, EVs may facilitate interactions between photoreceptors and Müller glia cells. In this review, we consider some of the proposed roles for EVs in retinal physiology and discuss current evidence regarding their potential impact on ocular therapies via gene or cell replacement strategies and direct intraocular administration in the diseased eye., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalargyrou, Guilfoyle, Smith, Ali and Pearson.)

Published
2023
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4. Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

Author

Youlten SE, Kemp JP, Logan JG, Ghirardello EJ, Sergio CM, Dack MRG, Guilfoyle SE, Leitch VD, Butterfield NC, Komla-Ebri D, Chai RC, Corr AP, Smith JT, Mohanty ST, Morris JA, McDonald MM, Quinn JMW, McGlade AR, Bartonicek N, Jansson M, Hatzikotoulas K, Irving MD, Beleza-Meireles A, Rivadeneira F, Duncan E, Richards JB, Adams DJ, Lelliott CJ, Brink R, Phan TG, Eisman JA, Evans DM, Zeggini E, Baldock PA, Bassett JHD, Williams GR, and Croucher PI

Subjects
Age Factors, Animals, Bone Diseases metabolism, Bone and Bones metabolism, Computational Biology, Female, Humans, Male, Mice, Mice, Knockout, Osteocytes cytology, Osteoporosis genetics, Sequence Analysis, RNA, Sex Factors, Bone Diseases genetics, Homeostasis, Osteocytes metabolism, Transcriptome
Abstract

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.

Published
2021
Full Text
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5. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

Author

McDonald MM, Khoo WH, Ng PY, Xiao Y, Zamerli J, Thatcher P, Kyaw W, Pathmanandavel K, Grootveld AK, Moran I, Butt D, Nguyen A, Corr A, Warren S, Biro M, Butterfield NC, Guilfoyle SE, Komla-Ebri D, Dack MRG, Dewhurst HF, Logan JG, Li Y, Mohanty ST, Byrne N, Terry RL, Simic MK, Chai R, Quinn JMW, Youlten SE, Pettitt JA, Abi-Hanna D, Jain R, Weninger W, Lundberg M, Sun S, Ebetino FH, Timpson P, Lee WM, Baldock PA, Rogers MJ, Brink R, Williams GR, Bassett JHD, Kemp JP, Pavlos NJ, Croucher PI, and Phan TG

Published
2021
Full Text
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