A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors.
Members of the Notch gene family have been shown to mediate cell-fate decisions by multipotent precursors in a number of different systems. To determine whether members of this family might play a similar role in hematopoiesis, we asked if homologues of the Notch gene are expressed in human hematopoietic precursors. Using degenerate oligonucleotides corresponding to conserved amino acid sequences in known Notch homologues as primers for the polymerase chain reaction (PCR), we demonstrated that at least one Notch homologue is expressed in human bone marrow CD34+ cells, a population enriched for hematopoietic precursors. Cloning and sequencing of the PCR products identified this Notch homologue as TAN-1, a member of the Notch family previously cloned from a T-cell leukemia with a translocation involving this gene. Subsequent evaluation of bone marrow hematopoietic cells for TAN-1 expression using a reverse transcription-PCR assay confirmed the expression of TAN-1 in CD34+ hematopoietic precursors, including the immature subset that lacks expression of lineage-associated antigens (CD34+lin-). These findings, together with the known role of Notch homologues in other systems, suggest that members of the Notch family, including TAN-1, may be involved in mediating cell-fate decisions during hematopoiesis.
Milner
L A
LA
Pediatric Oncology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Kopan
R
R
Martin
D I
DI
Bernstein
I D
ID
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001483:Base Sequence; D004330:Drosophila / Q000235:genetics*; D015870:Gene Expression; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors
D015703:Antigens, CD; D018952:Antigens, CD34; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors