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

Rouzanna Istvánffy, Baiba Vilne, Christina Schreck, Franziska Ruf, Charlotta Pagel, Sandra Grziwok, Lynette Henkel, Olivia Prazeres Da Costa, Johannes Berndt, Volker Stümpflen, Katharina S. Götze, Matthias Schiemann, Christian Peschel, Hans Werner Mewes, Robert A.J. Oostendorp

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Hematopoietic 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.

Original languageEnglish
Pages (from-to)702-715
Number of pages14
JournalStem Cell Reports
Volume5
Issue number5
DOIs
Publication statusPublished - 10 Nov 2015
Externally publishedYes

Field of Science*

  • 3.1 Basic medicine
  • 1.6 Biological sciences

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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