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  Extracellular matrix protein Matrilin-4 regulates stress-induced HSC proliferation via CXCR4

Uckelmann, H., Blaszkiewicz, S., Nicolae, C., Haas, S., Schnell, A., Wurzer, S., et al. (2016). Extracellular matrix protein Matrilin-4 regulates stress-induced HSC proliferation via CXCR4. Journal of Experimental Medicine, 213(10), 1961-1971. doi:10.1084/jem.20151713.

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Genre: Journal Article
Alternative Title : Brief Definitive Report

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 Creators:
Uckelmann, Hannah1, Author
Blaszkiewicz, Sandra1, Author
Nicolae, Claudia2, Author              
Haas, Simon1, Author
Schnell, Alexandra1, Author
Wurzer, Stephan1, Author
Wagener, Raimund1, Author
Aszodi, Attila2, Author              
Essers, Marieke Alida Gertruda1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; BONE-MARROW; MICE LACKING; QUIESCENT; CARTILAGE; RELEASE; DISEASE; ALPHA; NICHEImmunology; Research & Experimental Medicine;
 Abstract: During homeostasis, hematopoietic stem cells (HSCs) are mostly kept in quiescence with only minor contribution to steadystate hematopoiesis. However, in stress situations such as infection, chemotherapy, or transplantation, HSCs are forced to proliferate and rapidly regenerate compromised hematopoietic cells. Little is known about the processes regulating this stress-induced proliferation and expansion of HSCs and progenitors. In this study, we identified the extracellular matrix (ECM) adaptor protein Matrilin-4 (Matn4) as an important negative regulator of the HSC stress response. Matn4 is highly expressed in long-term HSCs; however, it is not required for HSC maintenance under homeostasis. In contrast, Matn4 is strongly down-regulated in HSCs in response to proliferative stress, and Matn4 deficiency results in increased proliferation and expansion of HSCs and progenitors after myelosuppressive chemotherapy, inflammatory stress, and transplantation. This enhanced proliferation is mediated by a transient down-regulation of CXCR4 in Matn4(-/-) HSCs upon stress, allowing for a more efficient expansion of HSCs. Thus, we have uncovered a novel link between the ECM protein Matn4 and cytokine receptor CXCR4 involved in the regulation of HSC proliferation and expansion under acute stress.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000384107700003
DOI: 10.1084/jem.20151713
 Degree: -

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Title: Journal of Experimental Medicine
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Rockefeller Institute for Medical Research
Pages: - Volume / Issue: 213 (10) Sequence Number: - Start / End Page: 1961 - 1971 Identifier: ISSN: 0022-1007
CoNE: https://pure.mpg.de/cone/journals/resource/954925413886