Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we examine the role of CD82/KAI1 in niche-mediated LT-HSC maintenance. We found that CD82/KAI1 is expressed predominantly on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs). In Cd82(-/-) mice, LT-HSCs were selectively lost as they exited from quiescence and differentiated. Mechanistically, CD82-based TGF-β1/Smad3 signaling leads to induction of CDK inhibitors and cell-cycle inhibition. The CD82 binding partner DARC/CD234 is expressed on macrophages and stabilizes CD82 on LT-HSCs, promoting their quiescence. When DARC(+) BM macrophages were ablated, the level of surface CD82 on LT-HSCs decreased, leading to cell-cycle entry, proliferation, and differentiation. A similar interaction appears to be relevant for human HSPCs. Thus, CD82 is a functional surface marker of LT-HSCs that maintains quiescence through interaction with DARC-expressing macrophages in the BM stem cell niche.

We present an integrated experimental and quantitative theoretical study of the mechanics of selfcrosslinked, neutral, repulsive pNIPAM microgel suspensions over a very wide range of concentrations ( ) that span the fluid, glassy and putative "soft jammed" regimes. In the glassy regime we measure a linear elastic dynamic shear modulus over 3 decades which follows an apparent power law concentration dependence ′~5.64 , a variation that appears distinct from prior studies of crosslinked ionic microgel suspensions. At very high concentrations there is a sharp crossover to a nearly linear growth of the modulus. To theoretically understand these observations, we formulate an approach to address all three regimes within a single conceptual Brownian dynamics framework. A minimalist single particle description is constructed that allows microgel size to vary with concentration due to steric de-swelling effects. Using a Hertzian repulsion interparticle potential and a suite of statistical mechanical theories, quantitative predictions under quiescent conditions of microgel collective structure, dynamic localization length, elastic modulus, and the structural relaxation time are made. Based on a constant interparticle repulsion strength parameter which is determined by requiring the theory to reproduce the linear elastic shear modulus over the entire concentration regime, we demonstrate good agreement between theory and experiment. Testable predictions are then made. We also measured nonlinear rheological properties with a focus on the yield stress and strain. A theoretical analysis with no adjustable parameters predicts how quiescent structural relaxation time changes under deformation, and how the yield stress and strain change as a function of concentration. Reasonable agreement with our observations is obtained. To the best of our knowledge, this is the first attempt to quantitatively understand structure, quiescent relaxation and shear elasticity, and nonlinear yielding of dense microgel suspensions using microscopic force based theoretical methods that include activated hopping processes. We expect our approach will be useful for other soft polymeric particle suspensions in the core-shell family. 3 I. IntroductionColloidal suspensions have been a major area of interest in the soft matter community for decades. Much fundamental research has been done with model hard-sphere colloids, with or without small polymer depletants, which have elucidated the understanding of physical phenomenon such as crystallization, phase separation, glassy dynamics, and nonlinear rheology [1][2][3]. Other widely studied systems are dense suspensions of soft colloids [4,5]. However, they bring additional complexities since the particles are deformable with a fluctuating internal polymeric microstructure, which can lead to their size and even shape becoming a function of thermodynamic state (volume fraction, temperature, ionic strength) and deformation. Most microgels are charged and can be created with diverse chemistry, which introduces con...