CD34 is a cell-surface sialomucin expressed by hematopoietic stem cells (HSC), mast cells, and vascular endothelia. Despite its popularity as an HSC marker, the function of CD34 on hematopoietic cells remains enigmatic. Here, we have addressed this issue by examining the behavior of mutant mast cells lacking CD34, the related sialomucin, CD43, or both molecules. Loss of these molecules leads to a gene-dose-dependent increase in mast cell homotypic aggregation with CD34/CD43KOs > CD43KO > CD34KO > wild-type. Importantly, reexpression of CD34 or CD43 in these cells caused reversal of this phenotype. Furthermore, we find that loss of these sialomucins prevents mast cell repopulation and hematopoietic precursor reconstitution in vivo. Our data provide clear-cut evidence for a hematopoietic function for CD34 and suggest that it acts as a negative regulator of cell adhesion.
Bibliographical noteFunding Information:
The authors wish to thank Dr. Stéphane Corbel for generation of cd34 −/− /cd43 −/− mice, Dr. Xuecui Guo for technical assistance with retroviral infections, Andrew Johnson for flow cytometry, and Shierley Chelliah for help with genotypic analysis. We would also like to thank Julie Chow in the Department of Pathology and Laboratory Services at the University of British Columbia for paraffin embedding and sectioning of tissues and Dr. Yukihiko Kitamura for generously providing us with antibodies toward SgIGSF. Lastly, we would like to extend our thanks to Dr. Michael Gurish for his technical advice for the limited dilution analysis and Dr. Sebastian Furness for his critical evaluation of the manuscript. K.M.M. is a Michael Smith Foundation for Health Research (MSFHR) and a Canadian Institute for Health Research (CIHR) Scholar and is a member of the Stem Cell Network Centre of Excellence. E.D. was supported by a Michael Smith Foundation for Health Research Trainee Scholarship and a Heart and Stroke Foundation Doctoral Scholarship. This work was funded by CIHR grant #117220 and #15477 and a grant in aid from the Heart and Stroke Foundation of British Columbia and the Yukon.
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases