Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-8-3
pubmed:abstractText
Notch and its ligands regulate multiple cell fate decisions. However, several questions on the timing, durability, and reversibility of Notch signaling effects on human hematopoietic precursors are still unresolved. Here, we used recombinant Delta ligands to deliver temporally and dose-controlled signals to human immature cord blood CD34(+)CD38(low) cells at clonal cell levels. Notch activation increased the frequency of multipotent progenitors, skewed the T and natural killer (NK) cell potential of CD34(+)CD38(low) clones in a dose- and ligand-dependent manner, and inhibited the differentiation of B cell clones. Low doses of ligands were sufficient for significantly increasing the frequency of NK cell precursors, whereas higher doses were required for increasing the frequency of T-cell clones. Interestingly, we demonstrate that temporary Notch activation prevents the subsequent differentiation of CD34(+)CD38(low) cells beyond a pro-B CD79a(+)CD19(-) stage characterized as a common lymphoid progenitor (CLP). Moreover, the lymphoid potential of this pro-B/CLP was skewed toward NK cell potential while the B cell precursor frequency was dramatically reduced. These results indicate critical timing and quantitative aspects of Notch/Delta interactions, imprinting the potential of CD34(+)CD38(low) hematopoietic progenitors. These results may have implications both in physiology and for cell manipulation because they demonstrate a tight regulation of the fate of human progenitors by Notch signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1676-85
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19544442-Animals, pubmed-meshheading:19544442-Antigens, CD34, pubmed-meshheading:19544442-Antigens, CD38, pubmed-meshheading:19544442-B-Lymphocytes, pubmed-meshheading:19544442-Cell Cycle, pubmed-meshheading:19544442-Cell Differentiation, pubmed-meshheading:19544442-Cell Line, pubmed-meshheading:19544442-Cells, Cultured, pubmed-meshheading:19544442-Fetal Blood, pubmed-meshheading:19544442-Flow Cytometry, pubmed-meshheading:19544442-Hematopoietic Stem Cells, pubmed-meshheading:19544442-Humans, pubmed-meshheading:19544442-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:19544442-Killer Cells, Natural, pubmed-meshheading:19544442-Membrane Proteins, pubmed-meshheading:19544442-Mice, pubmed-meshheading:19544442-Polymerase Chain Reaction, pubmed-meshheading:19544442-Receptors, Notch, pubmed-meshheading:19544442-T-Lymphocytes
pubmed:year
2009
pubmed:articleTitle
Notch increases T/NK potential of human hematopoietic progenitors and inhibits B cell differentiation at a pro-B stage.
pubmed:affiliation
INSERM, Unité U955, Créteil, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't