PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells

Ru Feng, Sabrina C. Desbordes, Huafeng Xie, Ester Sanchez Tillo, Fiona Pixley, E. Richard Stanley, Thomas Graf

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

Earlier work has shown that the transcription factor C/EBPα induced a transdifferentiation of committed lymphoid precursors into macrophages in a process requiring endogenous PU.1. Here we have examined the effects of PU.1 and C/EBPα on fibroblasts, a cell type distantly related to blood cells and akin to myoblasts, adipocytes, osteoblasts, and chondroblasts. The combination of the two factors, as well as PU.1 and C/EBPβ, induced the upregulation of macrophage/hematopoietic cell surface markers in a large proportion of NIH 3T3 cells. They also up-regulated these markers in mouse embryo- and adult skin-derived fibroblasts. Based on cell morphology, activation of macrophage-associated genes, and extinction of fibroblast-associated genes, cell lines containing an attenuated form of PU.1 and C/EBPα acquired a macrophage-like phenotype. The lines also display macrophage functions: They phagocytose small particles and bacteria, mount a partial inflammatory response, and exhibit strict CSF-1 dependence for growth. The myeloid conversion is primarily induced by PU.1, with C/EBPα acting as a modulator of macrophage-specific gene expression. Our data suggest that it might become possible to induce the transdifferentiation of skin-derived fibroblasts into cell types desirable for tissue regeneration.

Original languageEnglish
Pages (from-to)6057-6062
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number16
DOIs
Publication statusPublished - 22 Apr 2008

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