PMID- 21063023
OWN - NLM
STAT- MEDLINE
DCOM- 20110404
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 117
IP  - 6
DP  - 2011 Feb 10
TI  - The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood 
      CD34+ hematopoietic stem and progenitor cells.
PG  - 1840-50
LID - 10.1182/blood-2010-04-281329 [doi]
AB  - The stromal cell-derived factor-1 (SDF-1)/chemokine C-X-C receptor 4 (CXCR4) axis 
      plays a critical role in homing and engraftment of hematopoietic stem/progenitor 
      cells (HSCs) during bone marrow transplantation. To investigate the 
      transcriptional regulation provided by this axis, we performed the first 
      differential transcriptome profiling of human cord blood CD34(+) cells in 
      response to short-term exposure to SDF-1 and identified a panel of genes with 
      putative homing functions. We demonstrated that CD9, a member of the tetraspanin 
      family of proteins, was expressed in CD34(+)CD38(-/lo) and CD34(+)CD38(+) cells. 
      CD9 levels were enhanced by SDF-1, which simultaneously down-regulated CXCR4 
      membrane expression. Using specific inhibitors and activators, we demonstrated 
      that CD9 expression was modulated via CXCR4, G-protein, protein kinase C, 
      phospholipase C, extracellular signal-regulated kinase, and Janus kinase 2 
      signals. Pretreatment of CD34(+) cells with the anti-CD9 monoclonal antibody ALB6 
      significantly inhibited SDF-1-mediated transendothelial migration and calcium 
      mobilization, whereas adhesion to fibronectin and endothelial cells was enhanced. 
      Pretreatment of CD34(+) cells with ALB6 significantly impaired their homing to 
      bone marrow and spleen of sublethally irradiated NOD/SCID (nonobese 
      diabetic/severe combined immune-deficient) mice. Sorted CD34(+)CD9(-) cells 
      displayed lower bone marrow homing capacity compared with that of total CD34(+) 
      cells. CD9 expression on homed CD34(+) cells was significantly up-regulated in 
      vivo. Our results indicate that CD9 might possess specific functions in HSC 
      homing.
FAU - Leung, Kam Tong
AU  - Leung KT
AD  - Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong 
      Kong.
FAU - Chan, Kathy Yuen Yee
AU  - Chan KY
FAU - Ng, Pak Cheung
AU  - Ng PC
FAU - Lau, Tze Kin
AU  - Lau TK
FAU - Chiu, Wui Man
AU  - Chiu WM
FAU - Tsang, Kam Sze
AU  - Tsang KS
FAU - Li, Chi Kong
AU  - Li CK
FAU - Kong, Carrie Ka Lai
AU  - Kong CK
FAU - Li, Karen
AU  - Li K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101109
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD34)
RN  - 0 (CD9 protein, human)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Cd9 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Tetraspanin 29)
SB  - IM
CIN - Blood. 2011 Feb 10;117(6):1775-6. PMID: 21310932
CIN - Blood. 2011 May 26;117(21):5774-6. PMID: 21617010
MH  - Animals
MH  - Antibodies, Neutralizing
MH  - Antigens, CD/genetics/*physiology
MH  - Antigens, CD34/metabolism
MH  - Cell Adhesion/immunology/physiology
MH  - Cell Movement/immunology/physiology
MH  - Chemokine CXCL12/pharmacology
MH  - Fetal Blood/*cytology
MH  - Gene Expression Profiling
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/drug effects/*immunology/*physiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Membrane Glycoproteins/antagonists & inhibitors/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, CXCR4/physiology
MH  - Signal Transduction
MH  - Tetraspanin 29
MH  - Transplantation, Heterologous
EDAT- 2010/11/11 06:00
MHDA- 2011/04/05 06:00
CRDT- 2010/11/11 06:00
PHST- 2010/11/11 06:00 [entrez]
PHST- 2010/11/11 06:00 [pubmed]
PHST- 2011/04/05 06:00 [medline]
AID - S0006-4971(20)60301-9 [pii]
AID - 10.1182/blood-2010-04-281329 [doi]
PST - ppublish
SO  - Blood. 2011 Feb 10;117(6):1840-50. doi: 10.1182/blood-2010-04-281329. Epub 2010 
      Nov 9.