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Not just a marker: CD34 on human hematopoietic stem/progenitor cells dominates vascular selectin binding along with CD44

Dina B. AbuSamra, Fajr A. Aleisa, Asma S. Al-Amoodi, Heba M. Jalal Ahmed, Chee Jia Chin, Ayman F. Abuelela, Ptissam Bergam, Rachid Sougrat and Jasmeen S. Merzaban

Key Points

  • Human HSPCs expressing CD34 exhibit E-selectin binding activity, whereas those lacking CD34 do not.

  • CD34 is a unique E- and P-selectin ligand on human HSPCs that binds with kinetics comparable to other known selectin ligands.

Abstract

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.

  • Submitted May 2, 2017.
  • Accepted November 10, 2017.
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