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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.


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STEM CELLS IN HEMATOLOGY

Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins

Julia Beckmann1, Sebastian Scheitza1, Peter Wernet1, Johannes C. Fischer1, and Bernd Giebel1

1 Institute for Transplantation Diagnostics and Cellular Therapeutics, Heinrich-Heine-University Düsseldorf, Germany

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 cells (HSCs) and hematopoietic progenitor cells (HPCs) 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 HSCs/HPCs have the capability to divide asymmetrically, or whether the differences that have been observed are established by extrinsic mechanisms that act on postmitotic progenitors. Here, we have identified 4 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 HSCs/HPCs have the capability to divide asymmetrically. Remarkably, these proteins, in combination with the surrogate stem-cell marker CD133, help to discriminate the more primitive human cultivated HSCs/HPCs. Since 3 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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J. A. Martinez-Agosto, H. K.A. Mikkola, V. Hartenstein, and U. Banerjee
The hematopoietic stem cell and its niche: a comparative view
Genes & Dev., December 1, 2007; 21(23): 3044 - 3060.
[Abstract] [Full Text] [PDF]



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