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Istvanffy, R.* ; Kröger, M.* ; Eckl, C.* ; Gitzelmann, S.* ; Vilne, B.* ; Bock, F.* ; Graf, S.* ; Schiemann, M. ; Keller, U.B.* ; Peschel, C.* ; Oostendorp, R.A.*

Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells.

Blood 118, 2712-2722 (2011)
Verlagsversion Volltext DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 (Ptn(KD)) 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Growth-associated molecule; In-vivo; Beta-catenin; HB-Gam; Diverse functions; Binding-protein; Bone-formation; Self-renewal; Activation; Differentiation
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 118, Heft: 10, Seiten: 2712-2722 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Begutachtungsstatus Peer reviewed