@article{3442d78e71fb4cf785c01e7850ebb85d,
title = "Notch Signaling Specifies Megakaryocyte Development from Hematopoietic Stem Cells",
abstract = "In the hematopoietic system, Notch signaling specifies T cell lineage fate, in part through negative regulation of B cell and myeloid lineage development. However, we unexpectedly observed the development of megakaryocytes when using heterotypic cocultures of hematopoietic stem cells with OP9 cells expressing Delta-like1, but not with parental OP9 cells. This effect was abrogated by inhibition of Notch signaling either with γ-secretase inhibitors or by expression of the dominant-negative Mastermind-like1. The importance of Notch signaling for megakaryopoietic development in vivo was confirmed by using mutant alleles that either activate or inhibit Notch signaling. These findings indicate that Notch is a positive regulator of megakaryopoiesis and plays a more complex role in cell-fate decisions among myeloid progenitors than previously appreciated.",
keywords = "SIGNALING, STEMCELL",
author = "Thomas Mercher and Cornejo, {Melanie G.} and Christopher Sears and Thomas Kindler and Moore, {Sandra A.} and Ivan Maillard and Pear, {Warren S.} and Aster, {Jon C.} and Gilliland, {D. Gary}",
note = "Funding Information: We are very grateful to Dr. J.C. Z{\'u}{\~n}iga-Pfl{\"u}cker for the OP9-GFP and OP9-DL1 cells; Dr. C. Lavau for the ICN1, Hes1, and Hes5 constructs; and Dr. J.D. Griffin and Dr. Lizi Wu for the dnMAML1 construct. We are very grateful to Dr. O. Shestova and Dr. M. Santos for help with dnMAML1 transgenics. We thank A. Fabian for technical assistance with cell sorting and Dr. J.L. Kutok and the Dana Farber Histopathology Core Facility for histology studies. T.M. is a recipient of a Leukemia and Lymphoma Society Special Fellow Award. D.G.G. is a Doris Duke Foundation Distinguished Clinical Scientist and a Howard Hughes Medical Institute investigator. This work was supported in part by National Institute of Health grants AI047833 (W.S.P.), CA119070 (J.C.A.), and DK50654 and CA66996 (D.G.G.) and by the Leukemia and Lymphoma Society to W.S.P., J.C.A., and D.G.G. The authors declare no competing financial interests. ",
year = "2008",
month = sep,
day = "11",
doi = "10.1016/j.stem.2008.07.010",
language = "English",
volume = "3",
pages = "314--326",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "3",
}