Quantification of Self-Renewal Capacity in Single Hematopoietic Stem Cells from Normal and Lnk-Deficient Mice

• DOI: 10.1016/j.devcel.2005.03.019
• Publication Date: 2005-06-10T15:46:32Z
• Authors: Hideo Ema; Kazuhiro Sudo; Jun Seita; Azusa Matsubara; Yohei Morita; Mitsujiro Osawa; Kiyoshi Takatsu; Satoshi Takaki; Hiromitsu Nakauchi
• Keywords: Mice, Knockout; 0303 health sciences; Age Factors; Hematopoietic Stem Cell Transplantation; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Antigens, CD34; Bone Marrow Cells; Cell Count; Cell Differentiation; Flow Cytometry; Hematopoietic Stem Cells; Coculture Techniques; Clone Cells; Hematopoiesis; Mice; 03 medical and health sciences; Animals; Cells, Cultured; Developmental Biology; Adaptor Proteins, Signal Transducing; Bone Marrow Transplantation; Cell Proliferation

Despite being a hallmark of hematopoietic stem cells (HSCs), HSC self-renewal has never been quantitatively assessed. Establishment of a clonal and quantitative assay for HSC function permitted demonstration that adult mouse HSCs are significantly heterogeneous in degree of multilineage repopulation and that higher repopulating potential reflects higher self-renewal activity. An HSC with high repopulating potential could regenerate approximately 1000 HSCs, whereas the repopulating activity of regenerated HSCs on average was significantly reduced, indicating extensive but limited self-renewal capacity in HSCs. Comparisons of wild-type mice with mutant mice deficient in the signal adaptor molecule Lnk showed that not only HSC numbers but also the self-renewal capacity of some HSCs are markedly increased when Lnk function is lost. Lnk appears to control HSC numbers by negatively regulating HSC self-renewal signaling.