RRC ID 5417
Author Noda S, Horiguchi K, Ichikawa H, Miyoshi H.
Title Repopulating activity of ex vivo-expanded murine hematopoietic stem cells resides in the CD48-c-Kit+Sca-1+lineage marker- cell population.
Journal Stem Cells
Abstract A better understanding of the biology of cultured hematopoietic stem cells (HSCs) is required to achieve ex vivo expansion of HSCs. In this study, clonal analysis of the surface phenotype and repopulating activity of ex vivo-expanded murine HSCs was performed. After 7 days of culture with stem cell factor, thrombopoietin, fibroblast growth factor-1, and insulin-like growth factor-2, single CD34-/lowc-Kit+Sca-1+lineage marker- (CD34-KSL) cells gave rise to various numbers of cells. The proportion of KSL cells decreased with increasing number of expanded cells. Transplantation studies revealed that the progeny containing a higher percentage of KSL cells tended to have enhanced repopulating potential. We also found that CD48 was heterogeneously expressed in the KSL cell population after culture. Repopulating activity resided only in the CD48-KSL cell population, which had a relatively long intermitotic interval. Microarray analysis showed surprisingly few differences in gene expression between cultured CD48-KSL cells (cycling HSCs) and CD48+KSL cells (cycling non-HSCs) compared with freshly isolated CD34-KSL cells (quiescent HSCs), suggesting that the maintenance of stem cell activity is controlled by a relatively small number of genes. These findings should lead to a better understanding of ex vivo-expanded HSCs.
Volume 26(3)
Pages 646-55
Published 2008-3
DOI 10.1634/stemcells.2007-0623
PII 2007-0623
PMID 18079432
MeSH Animals Antigens, CD / metabolism* Ataxin-1 Ataxins Biomarkers / metabolism CD48 Antigen Cell Cycle / drug effects Cell Lineage* / drug effects Cell Proliferation / drug effects Clone Cells Cytokines / pharmacology Gene Expression Profiling Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / drug effects Kinetics Mice Mice, Inbred C57BL Nerve Tissue Proteins / metabolism* Nuclear Proteins / metabolism* Phenotype Proto-Oncogene Proteins c-kit / metabolism*
IF 5.587
Times Cited 24