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Name of Student:
Bernard Lo
Research Supervisor: Dr. Kelly McNagny
Title of Presentation: Podocalyxin Function in CXCL12-mediated Migration of Mouse
Hematopoietic Progenitor Cells
Abstract
CD34, podocalyxin (Podxl, gene name Podxl) and endoglycan comprise a family of cell surface
sialomucins with overlapping pattern of expression on hematopoietic precursors and vascular cells.
Although CD34 has long been used in the clinic as a marker of hematopoietic progenitors with longterm repopulation potential, little is known of the functions of CD34 sialomucins in vivo. In attempts to
define CD34-family functions, CD34 sialomucins have been shown to mediate pro- or anti-adhesive
functions related to tissue architecture or cell trafficking in both hematopoietic and non-hematopoietic
cell types. However, the molecular mechanisms underlying these putative functions remain enigmatic.
We have found that CD34 and Podxl promote the bone marrow-homing of definitive, hematopoietic
cells harvested from embryonic day 14.5 fetal liver (E14.5 FL-HSCs). To better characterize the
mechanisms underlying this function, we have identified a chemotactic defect in Podxl-deficient FLHSCs to stem cell factor (SCF) + CXCL12. In addition, Podxl co-localizes with CXCR4 and becomes
membrane-polarized in response to treatment with SCF + CXCL12. These data suggest that Podxl
enhances chemokine-dependent migration, perhaps by stabilizing the appropriate polarized expression
of chemokine receptors on the cell surface. Since Podxl deficient mice die at birth, we generated mice
with a hematopoietic tissue specific deletion of Podxl to further elucidate its function in vivo. Due to a
prospective defect in CXCL12 signaling associated with loss of Podxl, we examined AMD3100 (a
CXCR4 antagonists) mediated mobilization efficiency and susceptibility to 5-fluorouracil induced
myelosuppression. Although bone marrow progenitor cell mobilization is enhanced in Podxl-deficient
mice treated with AMD3100, they do not display evident sensitivity to myelotoxic stress. Thus,
podocalyxin may play a migratory-specific function in hematopoiesis. These results offer the first
mechanistic explanation for the cell-trafficking functions associated with the CD34-related
sialomucins.