TY - JOUR
T1 - The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype
AU - Morrison, Sean J.
AU - Weissman, Irving L.
N1 - Funding Information:
An abstract describing this work was presented at the Hematopoiesis, and Stem Cells Keystone Symposia, and is published in J. Cell. Bio-them. (1994) 18A:14 and 188:185. We thank A. Nicolau for technical assistance, V. Braunstein for antibody preparation, and L. Jerabek for capable laboratory management. Thanks to T. Knaak, J. Sun, D. Stovel, and M. Bigos for their operation of the FACS machines used in these experiments, and to L. Hidalgo and A. Salazar for animal care. S. M. is a Howard Hughes Medical Institute Predoctoral Fellow. This work was supported by National Cancer Institute grant number CA42551.
PY - 1994/11
Y1 - 1994/11
N2 - The Thy-1·1loSca-1hiLin-/lo population, representing 0.05% of C57BUKa-Thy-1.1 bone marrow, is highly enriched for hematopoietic stem cells and includes all multipotent progenitors in this mouse strain; however, the functional reconstituting activity of this fraction is heterogeneous. Only around 25% of clonal reconstitutions by cells from this population are long term; remaining clones yield transient multilineage reconstitutions. By fractionating based on lineage marker expression, the Thy-1·1loSca-1hiLin-/lo population has been resolved into three subpopulations: Lin-Mac-1-CD4-; Lin-Mac-1loCD4-; and Mac-1loCD4lo. Of these, only the Lin-Mac-1-CD4- population is highly enriched for long-term reconstituting hematopoietic stem cells. A comparison of transient and long-term multipotent progenitors indicates that long-term progenitors have less CFU-S activity, are equally radioprotective, and are less frequently in cell cycle. The ability to predict the longevity of reconstitution based on lineage marker expression indicates that reconstitution potential is deterministic, not stochastic.
AB - The Thy-1·1loSca-1hiLin-/lo population, representing 0.05% of C57BUKa-Thy-1.1 bone marrow, is highly enriched for hematopoietic stem cells and includes all multipotent progenitors in this mouse strain; however, the functional reconstituting activity of this fraction is heterogeneous. Only around 25% of clonal reconstitutions by cells from this population are long term; remaining clones yield transient multilineage reconstitutions. By fractionating based on lineage marker expression, the Thy-1·1loSca-1hiLin-/lo population has been resolved into three subpopulations: Lin-Mac-1-CD4-; Lin-Mac-1loCD4-; and Mac-1loCD4lo. Of these, only the Lin-Mac-1-CD4- population is highly enriched for long-term reconstituting hematopoietic stem cells. A comparison of transient and long-term multipotent progenitors indicates that long-term progenitors have less CFU-S activity, are equally radioprotective, and are less frequently in cell cycle. The ability to predict the longevity of reconstitution based on lineage marker expression indicates that reconstitution potential is deterministic, not stochastic.
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U2 - 10.1016/1074-7613(94)90037-X
DO - 10.1016/1074-7613(94)90037-X
M3 - Article
C2 - 7541305
AN - SCOPUS:0028534860
SN - 1074-7613
VL - 1
SP - 661
EP - 673
JO - Immunity
JF - Immunity
IS - 8
ER -