Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice.
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.
Ema
Hideo
H
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. hema@ims.u-tokyo.ac.jp
Sudo
Kazuhiro
K
Seita
Jun
J
Matsubara
Azusa
A
Morita
Yohei
Y
Osawa
Mitsujiro
M
Takatsu
Kiyoshi
K
Takaki
Satoshi
S
Nakauchi
Hiromitsu
H
D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D002999:Clone Cells / Q000187:drug effects / Q000637:transplantation; D018920:Coculture Techniques / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D011828:Radiation Chimera; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric
D048868:Adaptor Proteins, Signal Transducing; D018952:Antigens, CD34; D047908:Intracellular Signaling Peptides and Proteins; C490777:Lnk protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger