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Blood, 1 August 2001, Vol. 98, No. 3, pp. 513-524
PLENARY PAPER
Genomic and proteomic analysis of the myeloid
differentiation program
Zheng Lian,
Le Wang,
Shigeru Yamaga,
Wesley Bonds,
Y. Beazer-Barclay,
Yuval Kluger,
Mark Gerstein,
Peter E. Newburger,
Nancy Berliner, and
Sherman M. Weissman
From the Department of Genetics, Boyer Center for
Molecular Medicine, the Section of Hematology, Department of Internal
Medicine, and the Department of Molecular Biophysics and Biochemistry,
Yale University School of Medicine, New Haven, CT; the Department of
Pediatrics, University of Massachusetts Medical School, Worcester, MA;
and Gene Logic, Gaithersburg, MD.
Although the mature neutrophil is one of the better characterized
mammalian cell types, the mechanisms of myeloid differentiation are
incompletely understood at the molecular level. A mouse promyelocytic cell line (MPRO), derived from murine bone marrow cells and arrested developmentally by a dominant-negative retinoic acid receptor, morphologically differentiates to mature neutrophils in the presence of
10 µM retinoic acid. An extensive catalog was prepared of the gene
expression changes that occur during morphologic maturation. To do
this, 3'-end differential display, oligonucleotide chip array
hybridization, and 2-dimensional protein electrophoresis were used. A
large number of genes whose mRNA levels are modulated during
differentiation of MPRO cells were identified. The results suggest the
involvement of several transcription regulatory factors not previously
implicated in this process, but they also emphasize the importance of
events other than the production of new transcription factors.
Furthermore, gene expression patterns were compared at the level of
mRNA and protein, and the correlation between 2 parameters was studied.
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