Dataset Information

PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells.

ABSTRACT: Earlier work has shown that the transcription factor C/EBPalpha 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/EBPalpha 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/EBPbeta, induced the up-regulation 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/EBPalpha 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/EBPalpha 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.

SUBMITTER: Feng R

PROVIDER: S-EPMC2327209 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells.

Feng Ru R Desbordes Sabrina C SC Xie Huafeng H Tillo Ester Sanchez ES Pixley Fiona F Stanley E Richard ER Graf Thomas T

Proceedings of the National Academy of Sciences of the United States of America 20080418 16

Earlier work has shown that the transcription factor C/EBPalpha 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/EBPalpha 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/EBPbeta, induced the up-regulation of macrophage/hematopoietic cell surf ...[more]

PMID: 18424555

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Project description:BackgroundUnder aerobic conditions, acetic acid is the major byproduct produced by E. coli during the fermentation. And acetic acid is detrimental to cell growth as it destroys transmembrane pH gradients. Hence, how to reduce the production of acetic acid and how to utilize it as a feedstock are of intriguing interest. In this study, we provided an evidence to produce β-caryophyllene by the engineered E. coli using acetic acid as the only carbon source.ResultsFirstly, to construct the robust acetate-utilizing strain, acetyl-CoA synthases from three different sources were introduced and screened in the E. coli. Secondly, to establish the engineered strains converting acetic acid to β-caryophyllene, acetyl-CoA synthase (ACS), β-caryophyllene synthase (QHS1) and geranyl diphosphate synthase (GPPS2) were co-expressed in the E. coli cells. Thirdly, to further enhance β-caryophyllene production from acetic acid, the heterologous MVA pathway was introduced into the cells. What's more, acetoacetyl-CoA synthase (AACS) was also expressed in the cells to increase the precursor acetoacetyl-CoA and accordingly resulted in the increase of β-caryophyllene. The final genetically modified strain, YJM67, could accumulate the production of biomass and β-caryophyllene up to 12.6 and 1.05 g/L during 72 h, respectively, with a specific productivity of 1.15 mg h(-1) g(-1) dry cells, and the conversion efficiency of acetic acid to β-caryophyllene (gram to gram) reached 2.1%. The yield of β-caryophyllene on acetic acid of this strain also reached approximately 5.6% of the theoretical yield.ConclusionsIn the present study, a novel biosynthetic pathway for β-caryophyllene has been investigated by means of conversion of acetic acid to β-caryophyllene using an engineered Escherichia coli. This was the first successful attempt in β-caryophyllene production by E. coli using acetic acid as the only carbon source. Therefore, we have provided a new metabolic engineering tool for β-caryophyllene synthesis.

Dataset Information

PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells.

Publications

PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells.

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