Differentiation of inflammation-responsive astrocytes from glial progenitors generated from human induced pluripotent stem cells

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dc.authorid0000-0003-1106-3288
dc.contributor.authorSantos, Renata
dc.contributor.authorVadodaria, Krishna C.
dc.contributor.authorJaeger, Baptiste N.
dc.contributor.authorMei, Arianna
dc.contributor.authorLefcochilos-Fogelquist, Sabrina
dc.contributor.authorMendes, Ana P. D.
dc.contributor.authorErikson, Galina
dc.contributor.authorShokhirev, Maxim
dc.contributor.authorRandolph-Moore, Lynne
dc.contributor.authorFredlender, Callie
dc.contributor.authorDave, Sonia
dc.contributor.authorOefner, Ruth
dc.contributor.authorFitzpatrick, Conor
dc.contributor.authorPena, Monique
dc.contributor.authorBarron, Jerika J.
dc.contributor.authorKu, Manching
dc.contributor.authorDenli, Ahmet M.
dc.contributor.authorKerman, Bilal Ersen
dc.contributor.authorCharnay, Patrick
dc.contributor.authorKelsoe, John R.
dc.contributor.authorMarchetto, Maria C.
dc.contributor.authorGage, Fred H.
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:03:08Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:03:08Z
dc.date.issued2017
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.descriptionWOS: 000402964700027
dc.descriptionPubMed ID: 28591655
dc.description.abstractAstrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1 beta or tumor necrosis factor a elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1 beta. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration.
dc.description.sponsorshipPaul G. Allen Family Foundation; JPB Foundation; Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]; Annette C. Merle-Smith [R01 MH095741, U19MH106434]; G. Harold & Leila Y. Mathers Foundation; Flow Cytometry Core Facility of the Salk Institute; NIH-NCI CCSG [P30 014195]; Next Generation Sequencing Core Facility of the Salk Institute; Chapman Foundation; Helmsley Charitable Trust; Razavi Newman Integrative Genomics and Bioinformatics Core Facility of the Salk Institute; Swiss-NSF outgoing PD fellowship; Lynn and Edward Streim fellowship; EMBO long-term fellowship; Bettencourt Schueller Foundation; Philippe Foundation; Bob and Mary Jane Engmanen_US
dc.description.sponsorshipFor the production of the iPSCs, the authors would like to acknowledge financial support from Janssen Pharmaceuticals. This work was supported by the Paul G. Allen Family Foundation, Bob and Mary Jane Engman, The JPB Foundation, The Leona M. and Harry B. Helmsley Charitable Trust grant # 2012-PG-MED002, Annette C. Merle-Smith, R01 MH095741 (F.H.G.), U19MH106434 (F.H.G.), and The G. Harold & Leila Y. Mathers Foundation. This work was supported by the Flow Cytometry Core Facility of the Salk Institute with funding from NIH-NCI CCSG: P30 014195; the Next Generation Sequencing Core Facility of the Salk Institute with funding from NIH-NCI CCSG: P30 014195; the Chapman Foundation and the Helmsley Charitable Trust and by The Razavi Newman Integrative Genomics and Bioinformatics Core Facility of the Salk Institute with funding from NIH-NCI CCSG: P30 014195. This research was also supported by the Swiss-NSF outgoing PD fellowship (K.C.V.), Lynn and Edward Streim fellowship (K.C.V.), EMBO long-term fellowship (B.N.J.), the Bettencourt Schueller Foundation (B.N.J.), and the Philippe Foundation (B. N. J.). The authors would like to thank M. L. Gage for editorial comments.en_US
dc.identifier.citationSantos, R., Vadodaria, K. C., Jaeger, B. N., Mei, A., Lefcochilos-Fogelquist, S., Mendes, Ana P. D. ... Gage, F. H. (2017). Stem Cell Reports, 8(6), 1757-1769. https://dx.doi.org/10.1016/j.stemcr.2017.05.011
dc.identifier.doi10.1016/j.stemcr.2017.05.011
dc.identifier.endpage1769
dc.identifier.issn2213-6711
dc.identifier.issue6
dc.identifier.scopusqualityQ1
dc.identifier.startpage1757
dc.identifier.urihttps://dx.doi.org/10.1016/j.stemcr.2017.05.011
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3813
dc.identifier.volume8
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherCell Press
dc.relation.ispartofStem Cell Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectInflammation-Responsive Astrocytes
dc.subjectGlial Progenitors Generated
dc.subjectPluripotent Stem Cells
dc.titleDifferentiation of inflammation-responsive astrocytes from glial progenitors generated from human induced pluripotent stem cells
dc.typeArticle

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