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Cells 2019, 8(2), 131;

Gene Expression Profiling of NFATc1-Knockdown in RAW 264.7 Cells: An Alternative Pathway for Macrophage Differentiation

Institute of Biomedicine and Molecular Immunology “Alberto Monroy”, National Research Council, Via Ugo La Malfa 153, 90146 Palermo, Italy
Author to whom correspondence should be addressed.
Received: 13 December 2018 / Revised: 18 January 2019 / Accepted: 5 February 2019 / Published: 7 February 2019
(This article belongs to the Section Cell Nuclei: Function, Transport and Receptors)
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NFATc1, which is ubiquitous in many cell types, is the master regulator of osteoclastogenesis. However, the molecular mechanisms by which NFATc1 drives its transcriptional program to produce osteoclasts from macrophages (M) remains poorly understood. We performed quantitative PCR (QPCR) arrays and bioinformatic analyses to discover new direct and indirect NFATc1 targets. The results revealed that NFATc1 significantly modified the expression of 55 genes in untransfected cells and 31 genes after NFATc1-knockdown (≥2). Among them, we focused on 19 common genes that showed changes in the PCR arrays between the two groups of cells. Gene Ontology (GO) demonstrated that genes related to cell differentiation and the development process were significantly (p > 0.05) affected by NFATc1-knockdown. Among all the genes analyzed, we focused on GATA2, which was up-regulated in NFATc1-knockdown cells, while its expression was reduced after NFATc1 rescue. Thus, we suggest GATA2 as a new target of NFATc1. Ingenuity Pathway Analysis (IPA) identified up-regulated GATA2 and the STAT family members as principal nodes involved in cell differentiation. Mechanistically, we demonstrated that STAT6 was activated in parallel with GATA2 in NFATc1-knockdown cells. We suggest an alternative pathway for macrophage differentiation in the absence of NFATc1 due to the GATA2 transcription factor. View Full-Text
Keywords: NFATc1-knockdown; GATA2; STAT6; transcription factors; macrophages; osteoclasts NFATc1-knockdown; GATA2; STAT6; transcription factors; macrophages; osteoclasts

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Russo, R.; Mallia, S.; Zito, F.; Lampiasi, N. Gene Expression Profiling of NFATc1-Knockdown in RAW 264.7 Cells: An Alternative Pathway for Macrophage Differentiation. Cells 2019, 8, 131.

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