Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells

Rouzanna Istvanffy, Monika Kröger, Christina Eckl, Sylke Gitzelmann, Baiba Vilne, Franziska Bock, Steffi Graf, Matthias Schiemann, Ulrich B. Keller, Christian Peschel, Robert A.J. Oostendorp

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Pleiotrophin (Ptn) is strongly expressed by stromal cells which maintain HSCs. However, in vivo, Ptn deficiency does not alter steady-state hematopoiesis. However, knockdown of Ptn (PtnKD) in stromal cells increases production of hematopoietic progenitors as well as HSC activity in cocultures, suggesting that Ptn may have a role in HSC activation. Indeed, transplantations of wild-type (Ptn+/+) HSCs into Ptn-/- mice show increased donor cell production in serial transplantations and dominant myeloid regeneration caused by Ptn-dependent regulation of HSC repopulation behavior. This regulation of Lin-Kit +Sca1+ function is associated with increased proliferation and, on a molecular level, with up-regulated expression of cyclin D1 (Ccnd1) and C/EBPα (Cepba), but reduced of PPARγ. The known HSC regulator β-catenin is, however, not altered in the absence of Ptn. In conclusion, our results point to different Ptn-mediated regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration. Moreover, our results support the idea that microenvironmental Ptn regulates hematopoietic regeneration through β-catenin-independent regulation of Ccnd1 and Cebpa.

Original languageEnglish
Pages (from-to)2712-2722
Number of pages11
JournalBlood
Volume118
Issue number10
DOIs
Publication statusPublished - 8 Sep 2011
Externally publishedYes

Field of Science

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type

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

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