title: Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells.
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 (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.
authors.affiliation: III Department of Internal Medicine, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Rouzanna
authors.initials: R
authors.lastname: Istvanffy
authors.forename: Monika
authors.initials: M
authors.lastname: Kröger
authors.forename: Christina
authors.initials: C
authors.lastname: Eckl
authors.forename: Sylke
authors.initials: S
authors.lastname: Gitzelmann
authors.forename: Baiba
authors.initials: B
authors.lastname: Vilne
authors.forename: Franziska
authors.initials: F
authors.lastname: Bock
authors.forename: Steffi
authors.initials: S
authors.lastname: Graf
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.forename: Ulrich B
authors.initials: UB
authors.lastname: Keller
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Robert A J
authors.initials: RA
authors.lastname: Oostendorp
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C495267:CTNNB1 protein, mouse; D002352:Carrier Proteins; C530105:Ccnd1 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D051176:beta Catenin; C066845:pleiotrophin; D019938:Cyclin D1