Biopolis Dresden Imaging Platform

Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche.

Mitroulis I, Chen LS, Singh RP, Kourtzelis I, Economopoulou M, Kajikawa T, Troullinaki M, Ziogas A, Ruppova K, Hosur K, Maekawa T, Wang B, Subramanian P, Tonn T, Verginis P, von Bonin M, Wobus M, Bornhäuser M, Grinenko T, Di Scala M, Hidalgo A, Wielockx B, Hajishengallis G, Chavakis T

Hematopoietic stem cells (HSCs) remain mostly quiescent under steady-state conditions but switch to a proliferative state following hematopoietic stress, e.g., bone marrow (BM) injury, transplantation, or systemic infection and inflammation. The homeostatic balance between quiescence, self-renewal, and differentiation of HSCs is strongly dependent on their interactions with cells that constitute a specialized microanatomical environment in the BM known as the HSC niche. Here, we identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, we found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular (CAR) cells, and cells of the osteoblastic lineage. Del-1 promoted critical functions of the HSC niche, as it regulated long-term HSC (LT-HSC) proliferation and differentiation toward the myeloid lineage. Del-1 deficiency in mice resulted in reduced LT-HSC proliferation and infringed preferentially upon myelopoiesis under both steady-state and stressful conditions, such as hematopoietic cell transplantation and G-CSF- or inflammation-induced stress myelopoiesis. Del-1-induced HSC proliferation and myeloid lineage commitment were mediated by β3 integrin on hematopoietic progenitors. This hitherto unknown Del-1 function in the HSC niche represents a juxtacrine homeostatic adaptation of the hematopoietic system in stress myelopoiesis.

  • Clin Invest. 2017 Oct 2;127(10):3624-3639.
  • 2017
  • Cell Biology
  • 28846069
  • PubMed

Enabled by:

LMF & EMF CFCI

Back to list