Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development.
The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision. The validity of this model in the mouse has been questioned; however, little is known about the lineage potential of human progenitors. Here we provide a comprehensive analysis of the human hematopoietic hierarchy by clonally mapping the developmental potential of seven progenitor classes from neonatal cord blood and adult bone marrow. Human multilymphoid progenitors, identified as a distinct population of Thy-1(neg-lo)CD45RA(+) cells in the CD34(+)CD38(-) stem cell compartment, gave rise to all lymphoid cell types, as well as monocytes, macrophages and dendritic cells, which indicated that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation.
Doulatov
Sergei
S
Department of Stem Cell and Developmental Biology, Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
Notta
Faiyaz
F
Eppert
Kolja
K
Nguyen
Linh T
LT
Ohashi
Pamela S
PS
Dick
John E
JE
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000502:physiology; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000166:cytology / Q000502:physiology
D015703:Antigens, CD