C1qRp defines a new human stem cell population with hematopoietic and hepatic potential.
The characterization of two distinct classes of hematopoietic stem cells based on CD34 expression and the ability of human bone marrow (BM) cells to differentiate into nonhematopoietic cells introduced new levels of complexity within the stem cell compartment. Here we report the identification and purification of a rare human stem cell population with hematopoietic and hepatic potential based on the expression of a receptor for the complement molecule C1q (C1qR(p)). We show that C1qR(p) is a positive marker of all BM-repopulating stem cells because it is expressed on both CD34(-) and CD34(+) stem cells from umbilical cord blood and adult BM. In addition, we show that highly purified lineage-negative CD45(+)CD38(-)CD34(+or-)C1qR(p)(+) cells not only have BM-repopulating capacity but also can differentiate into human hepatocytes in vivo. The identification of human hepatocytes in mouse livers indicates that the NOD/SCID (nonobese diabetic/severe combined immunodeficient) mouse model can be a valuable tool to study the differentiation potential of adult human stem cells. These findings may have important scientific and clinical implications in the field of human stem cell biology and transplantation.
Danet
Guenahel H
GH
Howard Hughes Medical Institute and Abramson Family Cancer Research Institute, Molecular Cardiology Research Center, University of Pennsylvania School of Medicine, BRB-2/3, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Luongo
Jennifer L
JL
Butler
Gary
G
Lu
Min Min
MM
Tenner
Andrea J
AJ
Simon
M Celeste
MC
Bonnet
Dominique A
DA
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015415:Biomarkers; D002352:Carrier Proteins; D002454:Cell Differentiation; D006410:Hematopoiesis / Q000502:physiology*; D006411:Hematopoiesis, Extramedullary / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D018960:Hyaluronan Receptors; D008099:Liver / Q000166:cytology*; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D024101:Mitochondrial Proteins; D009244:NAD+ Nucleosidase; D011951:Receptors, Complement / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015415:Biomarkers; C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1