Long-term propagation of distinct hematopoietic differentiation programs in vivo.
Heterogeneity in the differentiation behavior of hematopoietic stem cells is well documented but poorly understood. To investigate this question at a clonal level, we isolated a subpopulation of adult mouse bone marrow that is highly enriched for multilineage in vivo repopulating cells and transplanted these as single cells, or their short-term clonal progeny generated in vitro, into 352 recipients. Of the mice, 93 showed a donor-derived contribution to the circulating white blood cells for at least 4 months in one of four distinct patterns. Serial transplantation experiments indicated that two of the patterns were associated with extensive self-renewal of the original cell transplanted. However, within 4 days in vitro, the repopulation patterns subsequently obtained in vivo shifted in a clone-specific fashion to those with less myeloid contribution. Thus, primitive hematopoietic cells can maintain distinct repopulation properties upon serial transplantation in vivo, although these properties can also alter rapidly in vitro.
Dykstra
Brad
B
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Kent
David
D
Bowie
Michelle
M
McCaffrey
Lindsay
L
Hamilton
Melisa
M
Lyons
Kristin
K
Lee
Shang-Jung
SJ
Brinkman
Ryan
R
Eaves
Connie
C
D053687:Adult Stem Cells / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D002999:Clone Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL