Stroma-derived connective tissue growth factor maintains cell cycle progression and repopulation activity of hematopoietic stem cells in vitro

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dc.contributor.authorIstvánffy, Rouzanna
dc.contributor.authorVilne, Baiba
dc.contributor.authorSchreck, Christina
dc.contributor.authorRuf, Franziska
dc.contributor.authorPagel, Charlotta
dc.contributor.authorGrziwok, Sandra
dc.contributor.authorHenkel, Lynette
dc.contributor.authorPrazeres Da Costa, Olivia
dc.contributor.authorBerndt, Johannes
dc.contributor.authorStümpflen, Volker
dc.contributor.authorGötze, Katharina S.
dc.contributor.authorSchiemann, Matthias
dc.contributor.authorPeschel, Christian
dc.contributor.authorMewes, Hans Werner
dc.contributor.authorOostendorp, Robert A.J.
dc.date.accessioned2021-04-30T06:15:01Z
dc.date.available2021-04-30T06:15:01Z
dc.date.issued2015-11-10
dc.descriptionFunding Information: This project was supported by Technische Universität München, Graduate School of Bioengineering (GSB; http://www.bioengineering.gs.tum.de ), the German José Leukemia Research Foundation (DJCLS R 11/12), and the German Research Council (DFG OO 8/5, OO 8/9, and FOR 2033/1). We gratefully acknowledge the support of Prof. Torsten Buch, of the Expression Core Facility of the Institute of Medical Microbiology, Hygiene, and Immunology of the Technische Universität München. Publisher Copyright: © 2015 The Authors. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
dc.description.abstractHematopoietic stem cells (HSCs) are preserved in co-cultures with UG26-1B6 stromal cells or their conditioned medium. We performed a genome-wide study of gene expression changes of UG26-1B6 stromal cells in contact with Lineage- SCA-1+ KIT+ (LSK) cells. This analysis identified connective tissue growth factor (CTGF) to be upregulated in response to LSK cells. We found that co-culture of HSCs on CTGF knockdown stroma (shCtgf) shows impaired engraftment and long-term quality. Further experiments demonstrated that CD34- CD48- CD150+ LSK (CD34- SLAM) cell numbers from shCtgf co-cultures increase in G0 and senescence and show delayed time to first cell division. To understand this observation, a CTGF signaling network model was assembled, which was experimentally validated. In co-culture experiments of CD34- SLAM cells with shCtgf stromal cells, we found that SMAD2/3-dependent signaling was activated, with increasing p27Kip1 expression and downregulating cyclin D1. Our data support the view that LSK cells modulate gene expression in the niche to maintain repopulating HSC activity.en
dc.description.statusPeer reviewed
dc.format.extent14
dc.format.extent3340420
dc.identifier.citationIstvánffy, R, Vilne, B, Schreck, C, Ruf, F, Pagel, C, Grziwok, S, Henkel, L, Prazeres Da Costa, O, Berndt, J, Stümpflen, V, Götze, K S, Schiemann, M, Peschel, C, Mewes, H W & Oostendorp, R A J 2015, 'Stroma-derived connective tissue growth factor maintains cell cycle progression and repopulation activity of hematopoietic stem cells in vitro', Stem Cell Reports, vol. 5, no. 5, pp. 702-715. https://doi.org/10.1016/j.stemcr.2015.09.018
dc.identifier.doi10.1016/j.stemcr.2015.09.018
dc.identifier.issn2213-6711
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/3996
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84946737661&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofStem Cell Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.1 Basic medicine
dc.subject1.6 Biological sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectBiochemistry
dc.subjectGenetics
dc.subjectDevelopmental Biology
dc.subjectCell Biology
dc.titleStroma-derived connective tissue growth factor maintains cell cycle progression and repopulation activity of hematopoietic stem cells in vitroen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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