CD44-mediated hyaluronan binding marks proliferating hematopoietic progenitor cells and promotes bone marrow engraftment

Abstract

CD44 is a widely expressed cell adhesion molecule that binds to the extracellular matrix component, hyaluronan. However, this interaction is not constitutive in most immune cells at steady state, as the ability of CD44 to engage hyaluronan is highly regulated. While activated T cells and macrophages gain the ability to bind hyaluronan by CD44, the status in other immune cells is less studied. Here we found a percentage of murine eosinophils, natural killer and natural killer T cells were capable of interacting with hyaluronan at steady state. To further investigate the consequences of hyaluronan binding by CD44 in the hematopoietic system, point mutations of CD44 that either cannot bind hyaluronan (LOF-CD44) or have an increased affinity for hyaluronan (GOF-CD44) were expressed in CD44-deficient bone marrow. Competitive bone marrow reconstitution of irradiated mice revealed an early preference for GOF-CD44 over WT-CD44 expressing cells, and for WT-CD44 over LOF-CD44 expressing cells, in the hematopoietic progenitor cell compartment. The advantage of the hyaluronan-binding cells was observed in the hematopoietic stem and progenitor populations, and was maintained throughout the immune system. Hematopoietic stem cells bound minimal hyaluronan at steady state, and this was increased when the cells were induced to proliferate whereas multipotent progenitors had an increased ability to bind hyaluronan at steady state. In vitro, the addition of hyaluronan promoted their proliferation. Thus, proliferating hematopoietic progenitors bind hyaluronan, and hyaluronan binding cells have a striking competitive advantage in bone marrow engraftment.

Evidence that hematopoietic stem cells in human umbilical cord blood is infectable by dengue virus: proposing a vertical transmission candidate

“…This result indicates that CD44 regulation may occur at the transcriptional level contributing to the early infection event However, how GATA-3 regulates HSC remains to be determined According to literature, GATA-3 is dispensable for HSC regulation and generation of early T cells [ 61 , 62 ]. It has been suggested that CD44 acts as an early marker of differentiation on immature cells CD34 + and supports HSC survival and maintenance of proliferating hematopoietic progenitor cells [ 63 , 64 , 65 ]. We observed a longitudinal increase in the CD44 rate among CD133 and CD34 cells from days 2–14 (Supplementary Figure S5D).…”

Sleep Deprivation Induces Cognitive Impairment by Increasing Blood-Brain Barrier Permeability via CD44

“…CD44, a receptor for the extracellular matrix component hyaluronan, is a widely expressed cell adhesion molecule (56). CD44 plays a vital role in different events involved in the inflammatory process and in several neurological disorders.…”

Intravascular heavy chain-modification of hyaluronan during endotoxic shock

“…We and others have previously shown that exogenous TSG-6 supplementation can improve hematopoietic progenitor cell function after cigarette smoke-induced myelosupression [16] and alter bone marrow stromal cell differentiation [26] , [27] , respectively. Additionally, a recent study revealed that CD44-HA binding interactions promote bone marrow progenitor proliferation and increase engraftment following irradiation [28] . Taken together, these findings emphasize the need for future studies to investigate the potential contributions of TSG-6 and HC-HA in the bone marrow during systemic inflammatory conditions that stress and mobilize the bone marrow compartment.…”