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Stepwise reprogramming of B cells into macrophages
Author(s): Xie HF, Ye M, Feng R, Graf T
Source: CELL    Volume: 117    Issue: 5    Pages: 663-676    Published: MAY 28 2004  
Times Cited: 175     References: 46     
Abstract: Starting with multipotent progenitors, hematopoietic lineages are specified by lineage-restricted transcription factors. The transcription factors that determine the decision between lymphoid and myeloid cell fates, and the underlying mechanisms, remain largely unknown. Here, we report that enforced expression of C/EBPalpha. and C/EBPbeta in differentiated B cells leads to their rapid and efficient reprogramming into macrophages. C/EBPs induce these changes by inhibiting the B cell commitment transcription factor Pax5, leading to the downregulation of its target CD19, and synergizing with endogenous PU.1, an ETS family factor, leading to the upregulation of its target Mac-1 and other myeloid markers. The two processes can be uncoupled, since, in PU.1-deficient pre-B cells, C/EBPs induce CD19 downregulation but not Mac-1 activation. Our observations indicate that C/EBPalpha and beta remodel the transcription network of B cells into that of macrophages through a series of parallel and sequential changes that require endogenous PU.1.
Document Type: Article
Language: English
Reprint Address: Graf, T (reprint author), Albert Einstein Coll Med, Ctr Canc Res, Dept Dev & Mol Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA
Addresses:
1. Albert Einstein Coll Med, Ctr Canc Res, Dept Dev & Mol Biol, Bronx, NY 10461 USA
Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: 826VP
ISSN: 0092-8674
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