Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties.
Hematopoietic stem cells (HSCs) execute self-renewal divisions throughout fetal and adult life, although some of their properties do alter. Here we analyzed the magnitude and timing of changes in the self-renewal properties and differentiated cell outputs of transplanted HSCs obtained from different sources during development. We also assessed the expression of several "stem cell" genes in corresponding populations of highly purified HSCs. Fetal and adult HSCs displayed marked differences in their self-renewal, differentiated cell output, and gene expression properties, with persistence of a fetal phenotype until 3 weeks after birth. Then, 1 week later, the HSCs became functionally indistinguishable from adult HSCs. The same schedule of changes in HSC properties occurred when HSCs from fetal or 3-week-old donors were transplanted into adult recipients. These findings point to the existence of a previously unrecognized, intrinsically regulated master switch that effects a developmental change in key HSC properties.
Bowie
Michelle B
MB
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3.
Kent
David G
DG
Dykstra
Brad
B
McKnight
Kristen D
KD
McCaffrey
Lindsay
L
Hoodless
Pamela A
PA
Eaves
Connie J
CJ
D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006413:Hematopoietic System / Q000196:embryology; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D018189:Immunomagnetic Separation; D007700:Kinetics; D008099:Liver / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological