Abstract
The Notch ligand, Jagged-1, plays an essential role in tissue formation during embryonic development of primitive organisms. However, little is known regarding the role of Jagged-1 in the regulation of tissue-specific stem cells or its function in humans. Here, we show that uncommitted human hematopoietic cells and cells that comprise the putative blood stem cell microenvironment express Jagged-1 and the Notch receptors. Addition of a soluble form of human Jagged-1 to cultures of purified primitive human blood cells had modest effects in augmenting cytokine-induced proliferation of progenitors. However, intravenous transplantation of cultured cells into immunodeficient mice revealed that human (h)Jagged-1 induces the survival and expansion of human stem cells capable of pluripotent repopulating capacity. Our findings demonstrate that hJagged-1 represents a novel growth factor of human stem cells, thereby providing an opportunity for the clinical utility of Notch ligands in the expansion of primitive cells capable of hematopoietic reconstitution.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD / analysis
-
Blood Cell Count
-
Calcium-Binding Proteins
-
Cell Division / drug effects
-
Cell Survival / drug effects
-
Cells, Cultured
-
Cytokines / pharmacology
-
Flow Cytometry
-
Gene Expression
-
Growth Substances / genetics
-
Growth Substances / metabolism
-
Growth Substances / pharmacology*
-
Hematopoiesis / drug effects
-
Hematopoietic Stem Cell Transplantation
-
Hematopoietic Stem Cells / cytology*
-
Hematopoietic Stem Cells / drug effects*
-
Hematopoietic Stem Cells / metabolism
-
Humans
-
Intercellular Signaling Peptides and Proteins
-
Jagged-1 Protein
-
Ligands
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Mice, Inbred NOD
-
Mice, SCID
-
Protein Binding
-
Proteins / genetics
-
Proteins / metabolism
-
Proteins / pharmacology*
-
RNA, Messenger / analysis
-
RNA, Messenger / genetics
-
Receptors, Notch
-
Serrate-Jagged Proteins
Substances
-
Antigens, CD
-
Calcium-Binding Proteins
-
Cytokines
-
Growth Substances
-
Intercellular Signaling Peptides and Proteins
-
JAG1 protein, human
-
Jag1 protein, mouse
-
Jagged-1 Protein
-
Ligands
-
Membrane Proteins
-
Proteins
-
RNA, Messenger
-
Receptors, Notch
-
Serrate-Jagged Proteins