The Notch Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro

被引:106
作者
Walker, L
Lynch, M
Silverman, S
Fraser, J
Boulter, J
Weinmaster, G
Gasson, JC
机构
[1] Univ Calif Los Angeles, Jonsson Comprehensive Canc Ctr, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA
[4] Univ Calif Los Angeles, Sch Med, Inst Mol Biol, Dept Biol Chem, Los Angeles, CA 90024 USA
关键词
Jagged1; Notch; hematopoiesis; stem cell factor; CD34(+) cells;
D O I
10.1002/stem.170162
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The cell surface receptor Notch1 is expressed on CD34(+) hematopoietic precursors, whereas one of its ligands, Jagged1, is expressed on bone marrow stromal cells. To examine the role of Notch signaling in early hematopoiesis, human CD34(+) cells were cultured in the presence or absence of exogenous cytokines on feeder layers that either did or did not express Jagged1. In the absence of recombinant growth factors, Jagged1 decreased myeloid colony formation by CD34(+) cells, as wed as H-3-thymidine incorporation and entry into S phase. In the presence of a strong cytokine signal to proliferate and mature, (interleukin 3 [IL-3] and IL-6, stem cell factor [SCF], and G-CSF), Jagged1 did not significantly alter either the fold expansion or the types of colonies formed by CD34(+) cells. However, in the presence of SCF alone, Jagged1 increased erythroid colony formation twofold. These results demonstrate that Notch can modulate a growth factor signal, and that in the absence of growth factor stimulation, the Jagged1-Notch pathway preserves CD34(+) cells in an immature state.
引用
收藏
页码:162 / 171
页数:10
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