Not just a marker: CD34 on human hematopoietic stem/progenitor cells dominates vascular selectin binding along with CD44
AuthorsAbu Samra, Dina Bashir Kamil
Aleisa, Fajr A
Al-Amoodi, Asma S.
Jalal Ahmed, Heba M.
Chin, Chee Jia
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Physical Sciences and Engineering (PSE) Division
Chemical and Biological Engineering Program
Imaging and Characterization Core Lab
KAUST Grant NumberCRG_R2_13_MERZ_KAUST_1
MetadataShow full item record
AbstractCD34 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.
CitationAbuSamra DB, Aleisa FA, Al-Amoodi AS, Jalal Ahmed HM, Chin CJ, et al. (2017) Not just a marker: CD34 on human hematopoietic stem/progenitor cells dominates vascular selectin binding along with CD44. Blood Advances 1: 2799–2816. Available: http://dx.doi.org/10.1182/bloodadvances.2017004317.
SponsorsThe 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.).
PublisherAmerican Society of Hematology
- Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells.
- Authors: Wan X, Sato H, Miyaji H, McDaniel JM, Wang Y, Kaneko E, Gibson B, Mehta-D'Souza P, Chen Y, Dozmorov M, Miller LP, Goodman J, Sun Z, Xia L
- Issue date: 2013 Oct
- P-Selectin coated microtube for enrichment of CD34+ hematopoietic stem and progenitor cells from human bone marrow.
- Authors: Narasipura SD, Wojciechowski JC, Charles N, Liesveld JL, King MR
- Issue date: 2008 Jan
- Functional selectin ligands mediating human CD34(+) cell interactions with bone marrow endothelium are enhanced postnatally.
- Authors: Hidalgo A, Weiss LA, Frenette PS
- Issue date: 2002 Aug
- Analysis of glycoprotein E-selectin ligands on human and mouse marrow cells enriched for hematopoietic stem/progenitor cells.
- Authors: Merzaban JS, Burdick MM, Gadhoum SZ, Dagia NM, Chu JT, Fuhlbrigge RC, Sackstein R
- Issue date: 2011 Aug 18
- Relationship between selectin-mediated rolling of hematopoietic stem and progenitor cells and progression in hematopoietic development.
- Authors: Greenberg AW, Kerr WG, Hammer DA
- Issue date: 2000 Jan 15