Differentiation Potential of Mesenchymal Stem/Stromal Cells Is Altered by Intrauterine Growth Restriction

Weatherall, Emma L; Avilkina, Viktorija; Cortes‐Araya, Yennifer; Dan-Jumbo, Susan O.; Stenhouse, Claire; Donadeu, F.X.; Esteves, Cristina L.

doi:10.3389/fvets.2020.558905

Cited by 15 publications

(17 citation statements)

References 62 publications

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“…Low birth weight piglets often display ‘catch up’ growth, but at the expense of laying down a higher proportion of body fat compared to normal sized littermates (Estany et al, 2017). Consistent with these observations, mesenchymal stem cells from intrauterine growth-restricted piglets show a differentiation bias towards the adipocyte lineage in comparison with their normal sized litter mates (Weatherall et al, 2020). Low birth weight piglets tend to produce fattier, less valuable carcasses from a production perspective and as such their incidence within pig litters should be kept to a minimum (Pardo et al, 2013).…”

Section: Introductionsupporting

confidence: 65%

Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions

Salavati

Woolley

Araya

et al. 2021

Preprint

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There is very little species-specific information about how the genome is regulated in domestic pigs (Sus scrofa). This lack of knowledge hinders efforts to define and predict the effects of genetic variants in pig breeding programmes. In order to address this knowledge gap, we need to identify regulatory sequences in the pig genome starting with regions of open chromatin. We have optimised the ‘Improved Protocol for the Assay for Transposase-Accessible Chromatin (Omni-ATAC-seq)’ to profile regions of open chromatin in flash frozen pig muscle tissue samples. This protocol has allowed us to identify putative regulatory regions in semitendinosus muscle from 24 male piglets. We collected samples from the smallest, average, and largest sized male piglets from each litter through five developmental time points. The ATAC-Seq data were mapped to Sscrofa11.1 with Bowtie2 and Genrich were used for post-alignment peak-calling. Of the 4661 putative regions of accessible chromatin identified, >50% were within 1 kb of known transcription start sites. The size of each open chromatin region varied according to the developmental time point. At day 90 of gestation, we investigated chromatin openness relative to foetal piglet size. In parallel we measured genome-wide gene expression and allele-specific expression using RNA-Seq analysis of the same muscle samples. We found regions of open chromatin associated with down regulation of genes involved in muscle development in small sized foetal piglets. The dataset that we have generated here provides: i) a resource for studies of genome regulation in pigs, and ii) contributes valuable functional annotation information to filter genetic variants for use in genomic selection in pig breeding programmes. Future work could leverage the ATAC-Seq data with very large datasets of genetic variants from phenotyped pigs. This approach could inform chromatin aware genomic prediction models and determine whether regions of open chromatin are enriched for trait-linked variants, and especially for muscle and meat traits.

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Section: Introductionsupporting

confidence: 65%

Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions

Salavati

Woolley

Araya

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Low birth weight piglets often display “catch up” growth, but at the expense of laying down a higher proportion of body fat compared to normal-sized littermates ( Estany et al 2017 ). Consistent with these observations, mesenchymal stem cells from intrauterine growth-restricted piglets show a differentiation bias toward the adipocyte lineage in comparison with their normal-sized litter mates ( Weatherall et al 2020 ). Low birth weight piglets tend to produce fatter, less valuable carcasses from a production perspective and as such their incidence within pig litters should be kept to a minimum ( Pardo et al 2013 ).…”

Section: Introductionsupporting

confidence: 63%

Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions

Salavati

Woolley

Araya

et al. 2021

G3 Genes|Genomes|Genetics

Self Cite

View full text Add to dashboard Cite

There is very little information about how the genome is regulated in domestic pigs (Sus scrofa). This lack of knowledge hinders efforts to define and predict the effects of genetic variants in pig breeding programmes. In order to address this knowledge gap, we need to identify regulatory sequences in the pig genome starting with regions of open chromatin. We used the ‘Improved Protocol for the Assay for Transposase-Accessible Chromatin (Omni-ATAC-Seq)’ to identify putative regulatory regions in flash frozen semitendinosus muscle from 24 male piglets. We collected samples from the smallest, average, and largest sized male piglets from each litter through five developmental time points. Of the 4,661 ATAC-Seq peaks identified that represent regions of open chromatin, >50% were within 1 kb of known transcription start sites. Differential read count analysis revealed 377 ATAC-Seq defined genomic regions where chromatin accessibility differed significantly across developmental time points. We found regions of open chromatin associated with down regulation of genes involved in muscle development that were present in small sized foetal piglets but absent in large foetal piglets at day 90 of gestation. The dataset that we have generated provides: a resource for studies of genome regulation in pigs, and contributes valuable functional annotation information to filter genetic variants for use in genomic selection in pig breeding programmes.

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“…The pathogenesis of that condition is not clear but is usually associated with placental insufficiency. The IUGR increases the risk of stillbirth, multiple congenital malformations, and even the incidence of type 2 diabetes and cardiovascular diseases in adulthood [12,23]. The results of a porcine study indicate that IUGR-MSCs show increased adipogenic and fibrogenic capacity.…”

Section: The Role Of the Placenta In Human Fetal Developmentmentioning

confidence: 99%

“…Their osteogenic and chondrogenic properties were significantly decreased compared to normal MSCs. The central hypothesis that comes from that study about the PD-MSCs' potential role in the pathophysiology of that condition is quite surprising and should be tested in humans [23].…”

Section: The Role Of the Placenta In Human Fetal Developmentmentioning

confidence: 99%

Human placenta-derived stem cells - recent findings based on the molecular science

Sibiak

Jaworski

Dorna

et al. 2020

Medical Journal of Cell Biology

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The human placenta is a complex, multifunctional transient fetomaternal organ. The placenta is composed of the maternal decidua basalis and its fetal part, consisting of the mesenchymal and trophoblast cell lineages. Both the placenta and the amniotic membranes are abundant in readily available placenta-derived mesenchymal stem cells (PD-MSCs). The clinical application of the PD-MSCs opens new perspectives for regenerative medicine and the treatment of various degenerative disorders. Their properties depend on their paracrine activity – the secretion of the anti-inflammatory cytokines and specific exosomes. In contrast to the PD-MSCs, the trophoblast stem cells (TSCs) are much more elusive. They can only be isolated from the blastocyst-stage embryos or the first-trimester placental tissue, making that procedure quite demanding. Also, other cultures require specific, strictly controlled conditions. TSCs may be potentially used as an in vitro model of various placental pathologies, facilitating the elucidation of their mysterious pathogenesis and creating the environment for testing the new drug efficiency. Nonetheless, it is unlikely that they could be ever implemented as a part of novel cellular therapeutic strategies in humans.Running title: Current knowledge on the placental stem cells

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Differentiation Potential of Mesenchymal Stem/Stromal Cells Is Altered by Intrauterine Growth Restriction

Cited by 15 publications

References 62 publications

Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions

Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions

Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions

Human placenta-derived stem cells - recent findings based on the molecular science

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