An old player, the right niche.

The cellular and molecular components of the niche for hematopoietic stem cells (HSCs) are still not well de fi ned. Angiopoietin-like proteins (Angptls) are a group of secreted glycoproteins that have been reported to play various roles, including the regulation of HSC activity. 1 Speci fi cally, Angptl2, a member of the Angptl family, was demonstrated to support HSC stemness through binding to inhibitory receptors. 2 Angptl2 has also been shown to support HSC activity in exosomes. 3 However, whether and how Angptl2 regulates HSC activities in the HSC niche were still unknown. Yu et al used an elegant approach to study these questions. 1 Based on the expression pattern of Angptl2 in bone marrow, several conditional knockout (KO) mice were generated to deplete Angptl2 from endothelial, mesenchymal stromal cells, megakaryocytes, and HSCs. Using a number of functional assays, including reconstitution analysis, fl ow cytometry, and immuno fl uorescence microscopy, the authors discovered that only endothelial cell-derived Angptl2 but not Angptl2 from other niche cell types supported the repopulation capacity, quiescent status, and niche localization of HSCs. They further demonstrated that Angptl2 enhances peroxisome-proliferator-activated receptor D expression to transactivate G0s2 and sustain the perinuclear localization of nucleolin that prevents HSCs from entering the cell cycle. study HSCs