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)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publication type
Article: Journal article
Document type
Scientific Article
Thesis type
Editors
Keywords
Growth-associated molecule; In-vivo; Beta-catenin; HB-Gam; Diverse functions; Binding-protein; Bone-formation; Self-renewal; Activation; Differentiation
Keywords plus
Language
english
Publication Year
2011
Prepublished in Year
HGF-reported in Year
2011
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
ISBN
Book Volume Title
Conference Title
Conference Date
Conference Location
Proceedings Title
Quellenangaben
Volume: 118,
Issue: 10,
Pages: 2712-2722
Article Number: ,
Supplement: ,
Series
Publisher
American Society of Hematology
Publishing Place
Day of Oral Examination
0000-00-00
Advisor
Referee
Examiner
Topic
University
University place
Faculty
Publication date
0000-00-00
Application date
0000-00-00
Patent owner
Further owners
Application country
Patent priority
Reviewing status
Peer reviewed
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-520100-001
G-520400-001
G-501790-003
Grants
Copyright
Erfassungsdatum
2011-12-31