c-Fos importance for brain development

Velazquez, Fabiola Noelia; Caputto, Beatriz L.; Boussin, François D.

doi:10.18632/aging.100862

Cited by 43 publications

(36 citation statements)

References 5 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, mutations in Fos/Jun genes were demonstrated during epidermal aging 48 . Third, Fos knockout mice exhibited a shortened life span of 6–7 months with growth retardation and severe osteoporosis 49 . These observations, together with our findings, indicate an involvement of FOS in regulating hMSC aging, as a downstream effector of ATF6 (Fig.…”

Section: Discussionmentioning

confidence: 99%

ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells

Wang¹,

Ding

et al. 2018

Cell Discov

View full text Add to dashboard Buy / Rent full text

Loss of organelle homeostasis is a hallmark of aging. However, it remains elusive how this occurs at gene expression level. Here, we report that human mesenchymal stem cell (hMSC) aging is associated with dysfunction of double-membrane organelles and downregulation of transcription factor ATF6. CRISPR/Cas9-mediated inactivation of ATF6 in hMSCs, not in human embryonic stem cells and human adipocytes, results in premature cellular aging, characteristic of loss of endomembrane homeostasis. Transcriptomic analyses uncover cell type-specific constitutive and stress-induced ATF6-regulated genes implicated in various layers of organelles’ homeostasis regulation. FOS was characterized as a constitutive ATF6 responsive gene, downregulation of which contributes to hMSC aging. Our study unravels the first ATF6-regulated gene expression network related to homeostatic regulation of membrane organelles, and provides novel mechanistic insights into aging-associated attrition of human stem cells.

show abstract

Section: Discussionmentioning

confidence: 99%

ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells

Wang¹,

Ding

et al. 2018

Cell Discov

View full text Add to dashboard Buy / Rent full text

show abstract

“…This family has been implicated as regulators of cell proliferation, differentiation, and transformation. FOS is a transcription factor which can heterodimerize with members of the Jun family to form the transcription factor activator protein 1 (AP-1) [ 20 ]. Original literature sources indicate presence of FOS transcripts in the germinal vesicle oocytes and meiosis II stage oocytes [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“Positive Regulation of RNA Metabolic Process” Ontology Group Highly Regulated in Porcine Oocytes Matured In Vitro: A Microarray Approach

Celichowski

Nawrocki

Dyszkiewicz-Konwińska

et al. 2018

BioMed Research International

View full text Add to dashboard Buy / Rent full text

The cumulus-oocyte complexes (COCs) growth and development during folliculogenesis and oogenesis are accompanied by changes involving synthesis and accumulation of large amount of RNA and proteins. In this study, the transcriptomic profile of genes involved in “oocytes RNA synthesis” in relation to in vitro maturation in pigs was investigated for the first time. The RNA was isolated from oocytes before and after in vitro maturation (IVM). Interactions between differentially expressed genes/proteins belonging to “positive regulation of RNA metabolic process” ontology group were investigated by STRING10 software. Using microarray assays, we found expression of 12258 porcine transcripts. Genes with fold change higher than |2| and with corrected p value lower than 0.05 were considered as differentially expressed. The ontology group “positive regulation of RNA metabolic process” involved differential expression of AR, INHBA, WWTR1, FOS, MEF2C, VEGFA, IKZF2, IHH, RORA, MAP3K1, NFAT5, SMARCA1, EGR1, EGR2, MITF, SMAD4, APP, and NR5A1 transcripts. Since all of the presented genes were downregulated after IVM, we suggested that they might be significantly involved in regulation of RNA synthesis before reaching oocyte MII stage. Higher expression of “RNA metabolic process” related genes before IVM indicated that they might be recognized as important markers and specific “transcriptomic fingerprint” of RNA template accumulation and storage for further porcine embryos growth and development.

show abstract

“…Fos is a subunit of the activator protein-1 TF (AP-1), a dimeric complex primarily containing members of the Fos and Jun factor families (Eferl and Wagner, 2003). As part of the AP-1 complex, Fos plays broad roles in proliferation, differentiation, and apoptosis, both in the context of development and tumorigenesis (Eferl and Wagner, 2003;Jochum et al, 2001;Velazquez et al, 2015). In addition, AP-1 functions to establish cell-type-specific enhancers and gene expression programs (Heinz et al, 2010;Vierbuchen et al, 2017), and to reconfigure enhancers during reprogramming to pluripotency (Knaupp et al, 2017;Madrigal and Alasoo, 2018).…”

Section: The Ap-1 Transcription Factor Subunit Fos Is Central To Reprmentioning

confidence: 99%

CellOracle: Dissecting cell identity via network inference and in silico gene perturbation

Kamimoto

Hoffmann

Morris

2020

Preprint

119

View full text Add to dashboard Buy / Rent full text

Here, we present CellOracle, a computational tool that integrates single-cell transcriptome and epigenome profiles to infer gene regulatory networks (GRNs), critical regulators of cell identity. Leveraging inferred GRNs, we simulate gene expression changes in response to transcription factor (TF) perturbation, enabling network configurations to be interrogated in silico, facilitating their interpretation. We validate the efficacy of CellOracle to recapitulate known regulatory changes across hematopoiesis, correctly predicting the outcomes of well-characterized TF perturbations. Integrating CellOracle analysis with lineage tracing of direct reprogramming reveals distinct network configurations underlying different reprogramming failure modes.Furthermore, analysis of GRN reconfiguration along successful reprogramming trajectories identifies new factors to enhance target cell yield, uncovering a role for the AP-1 subunit Fos, with the hippo signaling effector, Yap1. Together, these results demonstrate the efficacy of CellOracle to infer and interpret cell-type-specific GRN configurations, at high-resolution, promoting new mechanistic insights into the regulation and reprogramming of cell identity.

show abstract

c-Fos importance for brain development

Cited by 43 publications

References 5 publications

ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells

ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells

“Positive Regulation of RNA Metabolic Process” Ontology Group Highly Regulated in Porcine Oocytes Matured In Vitro: A Microarray Approach

CellOracle: Dissecting cell identity via network inference and in silico gene perturbation

Contact Info

Product

Resources

About