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

被引:108
作者
Beckmann, Julia [1 ]
Scheitza, Sebastian [1 ]
Wernet, Peter [1 ]
Fischer, Johannes C. [1 ]
Giebel, Bernd [1 ]
机构
[1] Univ Dusseldorf, Inst Transplantat Diagnost & Cellular Therapeut, D-4000 Dusseldorf, Germany
关键词
D O I
10.1182/blood-2006-11-055921
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 hernatopoletic stem cells (HSCs) and hernatopoletic 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 hernatopoietic 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 pro- teins, in combination with the surrogate stem-cell marker CD1 33, 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 endosomalassociated proteins, they may provide a link between the endosomal compartment and the process of asymmetric cell division within the HSC/HPC compartment.
引用
收藏
页码:5494 / 5501
页数:8
相关论文
共 43 条
[1]   CSL-independent Notch signalling: a checkpoint in cell fate decisions during development? [J].
Arias, AM ;
Zecchini, V ;
Brennan, K .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2002, 12 (05) :524-533
[2]   Weibel-Palade body membrane proteins exhibit differential trafficking after exocytosis in endothelial cells [J].
Arribas, M ;
Cutler, DF .
TRAFFIC, 2000, 1 (10) :783-793
[3]   Dare to be different:: Asymmetric cell division in Drosophila, C-elegans and vertebrates [J].
Betschinger, J ;
Knoblich, JA .
CURRENT BIOLOGY, 2004, 14 (16) :R674-R685
[4]   Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice [J].
Bhatia, M ;
Wang, JCY ;
Kapp, U ;
Bonnet, D ;
Dick, JE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5320-5325
[5]   Asymmetric cell divisions sustain long-term hematopoiesis from single-sorted human fetal liver cells [J].
Brummendorf, TH ;
Dragowska, W ;
Zijlmans, JMJM ;
Thornbury, G ;
Lansdorp, PM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (06) :1117-1124
[6]   Osteoblastic cells regulate the haematopoietic stem cell niche [J].
Calvi, LM ;
Adams, GB ;
Weibrecht, KW ;
Weber, JM ;
Olson, DP ;
Knight, MC ;
Martin, RP ;
Schipani, E ;
Divieti, P ;
Bringhurst, FR ;
Milner, LA ;
Kronenberg, HM ;
Scadden, DT .
NATURE, 2003, 425 (6960) :841-846
[7]   Exosome secretion:: The art of reutilizing nonrecycled proteins? [J].
de Gassart, A ;
Géminard, C ;
Hoekstra, D ;
Vidal, M .
TRAFFIC, 2004, 5 (11) :896-903
[8]   The tetraspanin CD63 enhances the internalization of the H,K-ATPase β-subunit [J].
Duffield, A ;
Kamsteeg, EJ ;
Brown, AN ;
Pagel, P ;
Caplan, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (26) :15560-15565
[9]   In vitro self-renewal division of hematopoietic stem cells [J].
Ema, H ;
Takano, H ;
Sudo, K ;
Nakauchi, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (09) :1281-1288
[10]   Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes [J].
Escola, JM ;
Kleijmeer, MJ ;
Stoorvogel, W ;
Griffith, JM ;
Yoshie, O ;
Geuze, HJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (32) :20121-20127