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Human notochordal cell transcriptome unveils potential regulators of cell function in the developing intervertebral disc

2018-08-27Journal article Open access
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dc.contributor.authorRodrigues-Pinto, Ricardo
dc.contributor.authorWard, L.
dc.contributor.authorHumphreys, M.
dc.contributor.authorZeef, L.
dc.contributor.authorBerry, A.
dc.contributor.authorHanley, K.
dc.contributor.authorHanley, N.
dc.contributor.authorRichardson, S.
dc.contributor.authorHoyland, J.
dc.date.accessioned2020-03-21T17:26:43Z
dc.date.available2020-03-21T17:26:43Z
dc.date.issued2018-08-27
dc.description.abstractThe adult nucleus pulposus originates from the embryonic notochord, but loss of notochordal cells with skeletal maturity in humans is thought to contribute to the onset of intervertebral disc degeneration. Thus, defining the phenotype of human embryonic/fetal notochordal cells is essential for understanding their roles and for development of novel therapies. However, a detailed transcriptomic profiling of human notochordal cells has never been achieved. In this study, the notochord-specific marker CD24 was used to specifically label and isolate (using FACS) notochordal cells from human embryonic and fetal spines (7.5-14 weeks post-conception). Microarray analysis and qPCR validation identified CD24, STMN2, RTN1, PRPH, CXCL12, IGF1, MAP1B, ISL1, CLDN1 and THBS2 as notochord-specific markers. Expression of these markers was confirmed in nucleus pulposus cells from aged and degenerate discs. Ingenuity pathway analysis revealed molecules involved in inhibition of vascularisation (WISP2, Noggin and EDN2) and inflammation (IL1-RN) to be master regulators of notochordal genes. Importantly, this study has, for the first time, defined the human notochordal cell transcriptome and suggests inhibition of inflammation and vascularisation may be key roles for notochordal cells during intervertebral disc development. The molecules and pathways identified in this study have potential for use in developing strategies to retard/prevent disc degeneration, or regenerate tissue.pt_PT
dc.description.sponsorshipThis research was funded by Arthritis Research UK (reference 21165 to SMR/JAH/LW) and the Henry Smith Charity (to JAH/SMR/MH). RRP was supported by a grant from the Programme for Advanced Medical Education, sponsored by Fundacão Calouste Gulbenkian, fundação Champalimaud, Ministério da Saúde, Fundação para a Ciência e Tecnologia and Apifarma, Portugal. Support was also received from the UK Medical Research Council (MR/J003352/1 to KPH), the Wellcome Trust (NAH was a senior fellow in clinical science, 088566; additional support from grant, 097820), and the British Council (14BX15NHBG to NAH). Consumable and technical support for this project (Sonal Patel) was funded by the National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. We are very grateful to all women who consented to take part in our research programme and for the assistance of research nurses and clinical colleagues at Manchester University NHS Foundation Trust. The authors would like to thank Prof Kathy Cheah and group for advice regarding the identification of sex-specific markers within microarray datasets.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRodrigues-Pinto R, Ward L, Humphreys M, et al. Human notochordal cell transcriptome unveils potential regulators of cell function in the developing intervertebral disc. Sci Rep. 2018;8(1):12866. Published 2018 Aug 27.pt_PT
dc.identifier.doi10.1038/s41598-018-31172-4pt_PT
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10400.16/2338
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Researchpt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-018-31172-4pt_PT
dc.titleHuman notochordal cell transcriptome unveils potential regulators of cell function in the developing intervertebral discpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage12866pt_PT
oaire.citation.titleScientific reportspt_PT
oaire.citation.volume8pt_PT
person.familyNameRodrigues-Pinto
person.givenNameRicardo
person.identifier.ciencia-id221F-996E-52A5
person.identifier.orcid0000-0002-6903-348X
person.identifier.scopus-author-id54981067800
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication40b26cca-90ca-47d6-9bbb-a14d37b9772c
relation.isAuthorOfPublication.latestForDiscovery40b26cca-90ca-47d6-9bbb-a14d37b9772c

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