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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5494-5501. Prepublished online as a Blood First Edition Paper on March 1, 2007; DOI 10.1182/blood-2006-11-055921.
Submitted November 2, 2006
Institute for Transplantation Diagnostics, & Cellular Therapeutics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany * Corresponding author; email: giebel{at}itz.uni-duesseldorf.de.
The findings that many primitive human hematopoietic cells give-rise to daughter cells that adopt different cell fates and/or show different proliferation kinetics, suggest that hematopoietic stem and progenitor cells (HSC/HPC) can divide asymmetrically. However, definitive experimental demonstration is lacking due to the current absence of asymmetrically segregating marker molecules within the primitive hematopoietic cell compartment. Thus, it remains an open question as to whether HSC/HPC have capabilities to divide asymmetrically, or whether the differences that have been observed are established by extrinsic mechanisms that act on post-mitotic progenitors. Here, we have identified four proteins (CD53; CD62L/L-selectin; CD63/lamp-3 and CD71/transferrin receptor) that segregate differentially in about 20% of primitive human hematopoietic cells that divide in stroma-free cultures. Therefore, this indicates for the first time that HSC/HPC have capabilities to divide asymmetrically. Remarkably, these proteins, in combination with the surrogate stem cell marker CD133, help to discriminate the more primitive human cultivated HSC/HPC. Since three of these proteins, the transferrin receptor and the tetraspanins CD53 and CD63, are endosomal-associated proteins, they may provide a link between the endosomal compartment and the process of asymmetric cell division within the HSC/HPC compartment.
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