PMID- 11724967
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 25
DP  - 2001 Dec 4
TI  - Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to 
      isolate long-term stem cells.
PG  - 14541-6
AB  - Clonogenic multipotent mouse hematopoietic stem cells (HSCs) and progenitor cells 
      are contained within the c-kit(+) (K) lineage(-/lo) (L) Sca-1(+) (S) population 
      of hematopoietic cells; long-term (LT) and short-term (ST) HSCs are Thy-1.1(lo). 
      c-kit is a member of the receptor tyrosine kinase family, a class of receptors 
      that are important in the proliferation and differentiation of hematopoietic 
      cells. To establish whether the Flk-2/Flt3 receptor tyrosine kinase was expressed 
      on the most primitive LT-HSCs, we sorted highly purified multipotent stem and 
      progenitor cells on the basis of Flk-2 surface expression and used them in 
      competitive reconstitution assays. Low numbers of Flk-2(-) HSCs gave rise to 
      long-term multilineage reconstitution in the majority of recipients, whereas the 
      transfer of Flk-2(+) multipotent cells resulted in mostly short-term multilineage 
      reconstitution. The KLS subset of adult mouse bone marrow was analyzed for Flk-2 
      and Thy-1.1 expression. Three phenotypically and functionally distinct 
      populations were isolated: Thy(lo) Flk-2(-) (LT-HSCs), Thy(lo) Flk-2(+) 
      (ST-HSCs), and Thy(-) Flk-2(+) multipotent progenitors. The loss of Thy-1.1 and 
      gain of Flk-2 expression marks the loss of self-renewal in HSC maturation. The 
      addition of Flk-2 antibody to the lineage mix allows direct isolation of LT-HSC 
      from adult bone marrow as c-kit(+) lin(-) Sca-1(+) Flk-2(-) from many strains of 
      mice. Fetal liver HSCs are contained within Flk-2(-) and Flk-2(+) KTLS cells.
FAU - Christensen, J L
AU  - Christensen JL
AD  - Departments of Pathology and Developmental Biology, Stanford University School of 
      Medicine, Stanford, CA 94305-5324, USA. juliech@stanford.edu
FAU - Weissman, I L
AU  - Weissman IL
LA  - eng
GR  - T32 AI007290/AI/NIAID NIH HHS/United States
GR  - P01 DK053074/DK/NIDDK NIH HHS/United States
GR  - CA42551/CA/NCI NIH HHS/United States
GR  - 5T32AI07290-16/AI/NIAID NIH HHS/United States
GR  - DK53074/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20011127
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, Ly)
RN  - 0 (Biomarkers)
RN  - 0 (Ly6a protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Thy-1 Antigens)
RN  - EC 2.7.10.1 (Flt3 protein, mouse)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Animals
MH  - Antigens, Ly/metabolism
MH  - Biomarkers
MH  - Cell Differentiation
MH  - Cell Separation/*methods
MH  - Fetus/cytology/immunology/metabolism
MH  - Hematopoiesis
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*cytology/immunology/*metabolism
MH  - Liver/cytology/immunology/metabolism
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Congenic
MH  - Mice, Inbred C57BL
MH  - Phenotype
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-kit/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Thy-1 Antigens/metabolism
MH  - fms-Like Tyrosine Kinase 3
PMC - PMC64718
EDAT- 2001/11/29 10:00
MHDA- 2002/01/11 10:01
PMCR- 2002/06/04
CRDT- 2001/11/29 10:00
PHST- 2001/11/29 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/11/29 10:00 [entrez]
PHST- 2002/06/04 00:00 [pmc-release]
AID - 261562798 [pii]
AID - 5627 [pii]
AID - 10.1073/pnas.261562798 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14541-6. doi: 10.1073/pnas.261562798. 
      Epub 2001 Nov 27.