Proposed model of the role of MT1-MMP–expressing niche cells, which serve as key links between the HIF-1 regulatory system and transcriptional regulation of vital niche chemokines/cytokines necessary for HSC maintenance and cell differentiation. MT1-MMP deficiency in niche cells up-regulates FIH1 expression, thereby preventing transcription of the HIF-responsive genes EPO, KitL, IL-7, and SDF-1α. MT1-MMP deficiency leads to impaired steady-state hematopoiesis because of a trilineage differentiation block.