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Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine

Overview of attention for article published in Stem Cell Research & Therapy, March 2023
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Title
Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine
Published in
Stem Cell Research & Therapy, March 2023
DOI 10.1186/s13287-023-03268-w
Pubmed ID
Authors

Alain Aguirre-Vázquez, Fabiola Castorena-Torres, Beatriz Silva-Ramírez, Katia Peñuelas-Urquides, María Elena Camacho-Moll, Luis A. Salazar-Olivo, Iván Velasco, Mario Bermúdez de León

Abstract

The generation of induced pluripotent stem cells has opened the field of study for stem cell research, disease modeling and drug development. However, the epigenetic signatures present in somatic cells make cell reprogramming still an inefficient process. This epigenetic memory constitutes an obstacle in cellular reprogramming. Here, we report the effect of hydralazine (HYD) and valproic acid (VPA), two small molecules with proven epigenetic activity, on the expression of pluripotency genes in adult (aHF) and neonatal (nbHF) human fibroblasts. aHF and nbHF were treated with HYD and/or VPA, and viability and gene expression assays for OCT4, NANOG, c-MYC, KLF4, DNMT1, TET3, ARID1A and ARID2 by quantitative PCR were performed. aHF and nbHF were transfected with episomal plasmid bearing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and exposed to HYD and VPA to determine the reprogramming efficiency. Methylation sensitive restriction enzyme (MSRE) qPCR assays were performed on OCT4 and NANOG promoter regions. Immunofluorescence assays were carried out for pluripotency genes on iPSC derived from aHF and nbHF. HYD upregulated the expression of OCT4 (2.5-fold) and NANOG (fourfold) genes but not c-Myc or KLF4 in aHF and had no significant effect on the expression of all these genes in nbHF. VPA upregulated the expression of NANOG (twofold) in aHF and c-MYC in nbHF, while it downregulated the expression of NANOG in nbHF. The combination of HYD and VPA canceled the OCT4 and NANOG overexpression induced by HYD in aHF, while it reinforced the effects of VPA on c-Myc expression in nbHF. The HYD-induced overexpression of OCT4 and NANOG in aHDF was not dependent on demethylation of gene promoters, and no changes in the reprogramming efficiency were observed in both cell populations despite the downregulation of epigenetic genes DNMT1, ARID1A, and ARID2 in nbHF. Our data provide evidence that HYD regulates the expression of OCT4 and NANOG pluripotency genes as well as ARID1A and ARID2 genes, two members of the SWI/SNF chromatin remodeling complex family, in normal human dermal fibroblasts.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 2 15%
Student > Bachelor 1 8%
Lecturer 1 8%
Researcher 1 8%
Unknown 8 62%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 23%
Sports and Recreations 1 8%
Neuroscience 1 8%
Unknown 8 62%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 March 2023.
All research outputs
#14,720,672
of 23,572,509 outputs
Outputs from Stem Cell Research & Therapy
#1,156
of 2,497 outputs
Outputs of similar age
#172,294
of 371,124 outputs
Outputs of similar age from Stem Cell Research & Therapy
#16
of 51 outputs
Altmetric has tracked 23,572,509 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,497 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 50% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 371,124 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 51 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.