CD34 is routinely used to identify and isolate human hematopoietic stem/progenitor cells (HSPCs) for use clinically in bone marrow transplantation, but its function on these cells remains elusive. Glycoprotein ligands on HSPCs help guide their migration to specialized microvascular beds in the bone marrow that express vascular selectins (E- and P-selectin). Here, we show that HSPC-enriched fractions from human hematopoietic tissue expressing CD34 (CD34pos) bound selectins, whereas those lacking CD34 (CD34neg) did not. An unbiased proteomics screen identified potential glycoprotein ligands on CD34pos cells revealing CD34 itself as a major vascular selectin ligand. Biochemical and CD34 knockdown analyses highlight a key role for CD34 in the first prerequisite step of cell migration, suggesting that it is not just a marker on these cells. Our results also entice future potential strategies to investigate the glycoforms of CD34 that discriminate normal HSPCs from leukemic cells and to manipulate CD34neg HSPC-enriched bone marrow or cord blood populations as a source of stem cells for clinical use.
|Original language||English (US)|
|Number of pages||18|
|State||Published - Dec 26 2017|
Bibliographical noteKAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): CRG_R2_13_MERZ_KAUST_1
Acknowledgements: The authors sincerely thank Samah Z. Gadhoum for her help and support throughout the project and Samir Hamdan for his time and fruitful discussions regarding the SPR analyses. The authors express their gratitude to Maryam Mih and Samar A. Rustum for their support in the management of the laboratory and also to Mohammad Imran Khan for his assistance with the confocal microscopy. Wei Xu at Imaging and Characterization core facility at King Abdullah University of Science and Technology (KAUST) was very helpful at providing analysis software and training on the confocal microscopes. The authors also thank Carolyn Unck from the KAUST Academic Writing Service for editing the manuscript. In addition, a special thanks to Aswini K. Panigrahi (MS assistance) and Alaguraj Dharmarajnadar (cell sorting on BD Influx) from the Bioscience Core Laboratory Facility at KAUST. This research was supported by a KAUST Faculty Baseline Research Funding Program and by a Competitive Research Grant (CRG_R2_13_MERZ_KAUST_1) (J.S.M.).