Universität zu Köln

Uckelmann, Hannah, Blaszkiewicz, Sandra, Nicolae, Claudia ORCID: 0000-0003-4933-5496, Haas, Simon ORCID: 0000-0001-9227-2051, Schnell, Alexandra, Wurzer, Stephan, Wagener, Raimund, Aszodi, Attila and Essers, Marieke Alida Gertruda (2016). Extracellular matrix protein Matrilin-4 regulates stress-induced HSC proliferation via CXCR4. J. Exp. Med., 213 (10). S. 1961 - 1972. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Uckelmann, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaszkiewicz, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Nicolae, Claudia UNSPECIFIED orcid.org/0000-0003-4933-5496 UNSPECIFIED Haas, Simon UNSPECIFIED orcid.org/0000-0001-9227-2051 UNSPECIFIED Schnell, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Wurzer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, Raimund UNSPECIFIED UNSPECIFIED UNSPECIFIED Aszodi, Attila UNSPECIFIED UNSPECIFIED UNSPECIFIED Essers, Marieke Alida Gertruda UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-264362
DOI:	10.1084/jem.20151713
Journal or Publication Title:	J. Exp. Med.
Volume:	213
Number:	10
Page Range:	S. 1961 - 1972
Date:	2016
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-9538
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; BONE-MARROW; MICE LACKING; QUIESCENT; CARTILAGE; RELEASE; DISEASE; ALPHA; NICHE Multiple languages Immunology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26436