Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells.
Long-term hematopoietic stem cells (HSCs [LT-HSCs]) are well known to display unpredictable differences in their clonal expansion capacities after transplantation. Here, by analyzing the cellular output after transplantation of stem cells differing in surface expression levels of the Kit receptor, we show that LT-HSCs can be systematically subdivided into two subtypes with distinct reconstitution behavior. LT-HSCs expressing intermediate levels of Kit receptor (Kit(int)) are quiescent in situ but proliferate extensively after transplantation and therefore repopulate large parts of the recipient's hematopoietic system. In contrast, metabolically active Kit(hi) LT-HSCs display more limited expansion capacities and show reduced but robust levels of repopulation after transfer. Transplantation into secondary and tertiary recipient mice show maintenance of efficient repopulation capacities of Kit(int) but not of Kit(hi) LT-HSCs. Initiation of differentiation is marked by the transit from Kit(int) to Kit(hi) HSCs, both of which precede any other known stem cell population.
Regeneration in Hematopoiesis Laboratory, Center for Regenerative Therapies Dresden; and 2 Deep Sequencing Group SFB 655, Biotechnology Center; Dresden University of Technology, 01307 Dresden, Germany.
Tatyana
T
Grinenko
Kathrin
K
Arndt
Melanie
M
Portz
Nicole
N
Mende
Marko
M
Günther
Kadriye Nehir
KN
Cosgun
Dimitra
D
Alexopoulou
Naharajan
N
Lakshmanaperumal
Ian
I
Henry
Andreas
A
Dahl
Claudia
C
Waskow
D000818:Animals; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction
D019009:Proto-Oncogene Proteins c-kit