Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins.
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.
Beckmann
Julia
J
Institute for Transplantation Diagnostics and Cellular Therapeutics, Heinrich-Heine-University Düsseldorf, Germany.
Scheitza
Sebastian
S
Wernet
Peter
P
Fischer
Johannes C
JC
Giebel
Bernd
B
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D002451:Cell Compartmentation; D002455:Cell Division; D002478:Cells, Cultured; D011992:Endosomes; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D019041:L-Selectin; D010980:Platelet Membrane Glycoproteins; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D011990:Receptors, Transferrin; D060265:Tetraspanin 25; D060149:Tetraspanin 30
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; C554894:CD53 protein, human; C554586:CD63 protein, human; C068126:CD71 antigen; D010980:Platelet Membrane Glycoproteins; D011506:Proteins; D011990:Receptors, Transferrin; D060265:Tetraspanin 25; D060149:Tetraspanin 30; D019041:L-Selectin