PMID- 17016561
OWN - NLM
STAT- MEDLINE
DCOM- 20070105
LR  - 20220331
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 116
IP  - 10
DP  - 2006 Oct
TI  - Hematopoietic stem cells proliferate until after birth and show a reversible 
      phase-specific engraftment defect.
PG  - 2808-16
AB  - The regulation of HSC proliferation and engraftment of the BM is an important but 
      poorly understood process, particularly during ontogeny. Here we show that in 
      mice, all HSCs are cycling until 3 weeks after birth. Then, within 1 week, most 
      became quiescent. Prior to 4 weeks of age, the proliferating HSCs with long-term 
      multilineage repopulating activity displayed an engraftment defect when 
      transiting S/G2/M. During these cell cycle phases, their expression of CXC 
      chemokine ligand 12 (CXCL12; also referred to as stromal cell-derived factor 1 
      [SDF-1]) transiently increased. The defective engrafting activity of HSCs in 
      S/G2/M was reversed when cells were allowed to progress into G1 prior to 
      injection or when the hosts (but not the cells) were pretreated with a CXCL12 
      antagonist. Interestingly, the enhancing effect of CXCL12 antagonist pretreatment 
      was exclusive to transplants of long-term multilineage repopulating HSCs in 
      S/G2/M. These results demonstrate what we believe to be a new HSC regulatory 
      checkpoint during development. They also suggest an ability of HSCs to express 
      CXCL12 in a fashion that changes with cell cycle progression and is associated 
      with a defective engraftment that can be overcome by in vivo administration of a 
      CXCL12 antagonist.
FAU - Bowie, Michelle B
AU  - Bowie MB
AD  - Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada.
FAU - McKnight, Kristen D
AU  - McKnight KD
FAU - Kent, David G
AU  - Kent DG
FAU - McCaffrey, Lindsay
AU  - McCaffrey L
FAU - Hoodless, Pamela A
AU  - Hoodless PA
FAU - Eaves, Connie J
AU  - Eaves CJ
LA  - eng
GR  - P01 HL055435/HL/NHLBI NIH HHS/United States
GR  - P01 HL-55435/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 143198-26-9 (Integrin alpha4)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - U3P01618RT (Fluorouracil)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
CIN - J Clin Invest. 2006 Oct;116(10):2593-6. PMID: 17016556
MH  - Animals
MH  - Animals, Newborn
MH  - Bone Marrow Cells/cytology/drug effects/metabolism
MH  - Cell Cycle/drug effects/physiology
MH  - *Cell Proliferation
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/antagonists & inhibitors/genetics
MH  - Fluorouracil/pharmacology
MH  - Gene Expression/genetics
MH  - Graft Survival/drug effects/physiology
MH  - Hematopoiesis/drug effects/physiology
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*cytology/drug effects/metabolism
MH  - Hematopoietic System/*cytology/embryology/growth & development
MH  - Hyaluronan Receptors/genetics
MH  - Integrin alpha4/genetics
MH  - Liver/cytology/drug effects/embryology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Proto-Oncogene Proteins c-kit/genetics
MH  - Receptors, CXCR4/genetics
MH  - Thymidine/pharmacology
MH  - Vascular Cell Adhesion Molecule-1/genetics
PMC - PMC1578623
EDAT- 2006/10/04 09:00
MHDA- 2007/01/06 09:00
PMCR- 2006/10/02
CRDT- 2006/10/04 09:00
PHST- 2006/02/21 00:00 [received]
PHST- 2006/07/11 00:00 [accepted]
PHST- 2006/10/04 09:00 [pubmed]
PHST- 2007/01/06 09:00 [medline]
PHST- 2006/10/04 09:00 [entrez]
PHST- 2006/10/02 00:00 [pmc-release]
AID - 28310 [pii]
AID - 10.1172/JCI28310 [doi]
PST - ppublish
SO  - J Clin Invest. 2006 Oct;116(10):2808-16. doi: 10.1172/JCI28310.