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Article: Directed Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells

TitleDirected Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells
Authors
Keywordshuman induced pluripotent stem cells
intervertebral disc disease
nucleus pulposus (NP)-like cells
notochord-like cells (NCLs)
directed differentiation
Issue Date2020
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports
Citation
Cell Reports, 2020, v. 30 n. 8, p. 2791-2806.e5 How to Cite?
AbstractIntervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-β pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration.
Persistent Identifierhttp://hdl.handle.net/10722/283700
ISSN
2019 Impact Factor: 8.109
2015 SCImago Journal Rankings: 8.588

 

DC FieldValueLanguage
dc.contributor.authorZhang, Y-
dc.contributor.authorZHANG, Z-
dc.contributor.authorChen, P-
dc.contributor.authorMA, CY-
dc.contributor.authorLi, C-
dc.contributor.authorAu, TYK-
dc.contributor.authorTam, V-
dc.contributor.authorPeng, Y-
dc.contributor.authorWu, R-
dc.contributor.authorCheung, KMC-
dc.contributor.authorSham, PC-
dc.contributor.authorTse, HF-
dc.contributor.authorChan, D-
dc.contributor.authorLeung, VY-
dc.contributor.authorCheah, KSE-
dc.contributor.authorLian, Q-
dc.date.accessioned2020-07-03T08:22:52Z-
dc.date.available2020-07-03T08:22:52Z-
dc.date.issued2020-
dc.identifier.citationCell Reports, 2020, v. 30 n. 8, p. 2791-2806.e5-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10722/283700-
dc.description.abstractIntervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-β pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports-
dc.relation.ispartofCell Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjecthuman induced pluripotent stem cells-
dc.subjectintervertebral disc disease-
dc.subjectnucleus pulposus (NP)-like cells-
dc.subjectnotochord-like cells (NCLs)-
dc.subjectdirected differentiation-
dc.titleDirected Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells-
dc.typeArticle-
dc.identifier.emailChen, P: pkchen@hku.hk-
dc.identifier.emailAu, TYK: tiffany_au@hku.hk-
dc.identifier.emailTam, V: vivtam@hku.hk-
dc.identifier.emailCheung, KMC: cheungmc@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailChan, D: chand@hku.hk-
dc.identifier.emailLeung, VY: vicleung@hku.hk-
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hk-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.authorityCheung, KMC=rp00387-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authorityChan, D=rp00540-
dc.identifier.authorityLeung, VY=rp01764-
dc.identifier.authorityCheah, KSE=rp00342-
dc.identifier.authorityLian, Q=rp00267-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2020.01.100-
dc.identifier.pmid32101752-
dc.identifier.scopuseid_2-s2.0-85079900835-
dc.identifier.hkuros310722-
dc.identifier.volume30-
dc.identifier.issue8-
dc.identifier.spage2791-
dc.identifier.epage2806.e5-
dc.publisher.placeUnited States-

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