Short heat shock has a long-term effect on mesenchymal stem cells’ transcriptome
. bioRxiv 2022
. Publisher's VersionAbstract
Background: Mesenchymal stem cells (MSCs) are multipotent stromal, non-hematopoietic cells with self-renewal and differentiation properties and are therefore a preferred source for cellular therapies. However, a better understanding of culture techniques is required to harness their full potential. Here we aim to compare the effects of short and long heat shock (HS) on the transcriptomic landscape of MSCs. Methods: MSCs were extracted from the umbilical cord of a bovine fetus, cultured, and validated as MSCs. Early passage cells were exposed to 40.5°C for six hours or three days. RNA sequencing and bioinformatics analysis were performed to systematically examine the transcriptional changes following each treatment and to identify specific biological features and processes. Results: The data indicates that while long heat stress influences many cell processes, such as immune response, cell cycle, and differentiation, the short HS mostly upregulates the cellular stress response. Once normothermia is resumed the long-term effects of the short HS can be revealed: although most genes revert to their original expression levels, a subgroup of epigenetically marked genes termed bivalent genes, maintains high expression levels. These genes are known to support cell lineage specification and are carefully regulated by a group of chromatin modifiers. One family of those chromatin modifiers, called MLL genes, is highly over-represented in the transiently upregulated cluster after six hours of HS. Therefore, our data provide a mechanistic explanation for the long-term phenotype of short HS on development-related genes and could be used to predict the long-term effect of HS on cell identity. Conclusions: Understanding the influence of culture conditions on morphology, phenotype, proliferative capacity, and fate decision of MSCs is needed to optimize culture conditions suitable for clinical or commercial use. Here, we suggest that simple and short stress can alter the cell’s proliferation and differentiation capacities and, therefore, following future optimizations, be used to shift the cells toward a more desirable functionality.Competing Interest StatementThe authors have declared no competing interest.
Establishing and using a genetic database for resolving identification of fish species in the Sea of Galilee, Israel
. PLOS ONE 2022
, 1-17. Publisher's VersionAbstract
Freshwaters are a very valuable resource in arid areas, such as Mediterranean countries. Freshwater systems are vulnerable ecological habitats, significantly disturbed globally and especially in arid areas. The Sea of Galilee is the largest surface freshwater body in the Middle East. It is an isolated habitat supporting unique fish populations, including endemic species and populations on the edge of their distribution range. Using the Sea of Galilee for water supply, fishing and recreation has been placing pressure on these fish populations. Therefore, efficient monitoring and effective actions can make a difference in the conservation of these unique fish populations. To set a baseline and develop molecular tools to do so, in this study, DNA barcoding was used to establish a database of molecular species identification based on sequences of Cytochrome C Oxidase subunit I gene. DNA barcodes for 22 species were obtained and deposited in Barcode of Life Database. Among these, 12 barcodes for 10 species were new to the database and different from those already there. Barcode sequences were queried against the database and similar barcodes from the same and closely related species were obtained. Disagreements between morphological and molecular species identification were identified for five species, which were further studied by phylogenetic and genetic distances analyses. These analyses suggested the Sea of Galilee contained hybrid fish of some species and other species for which the species definition should be reconsidered. Notably, the cyprinid fish defined as Garra rufa, should be considered as Garra jordanica. Taken together, along with data supporting reconsideration of species definition, this study sets the basis for further using molecular tools for monitoring fish populations, understanding their ecology, and effectively managing their conservation in this unique and important habitat and in the region.
Interferon-Tau regulates a plethora of functions in the corpus luteum
. DOMESTIC ANIMAL ENDOCRINOLOGY 2022
The corpus luteum (CL) plays a vital role in regulating the reproductive cycle, fertility, and in maintaining pregnancy. Interferon-tau (IFNT) is the maternal recognition of a pregnancy signal in domestic ruminants; its uterine, paracrine actions, which extend the CL lifespan, are widely established. However, considerable evidence also suggests a direct, endocrine role for IFNT. The purpose of this review is to highlight the importance of IFNT in CL main-tenance, acting directly and in a cell-specific manner. A transcriptomic study revealed a distinct molecular profile of IFNT-exposed day 18, pregnant bovine CL, compared to the non-pregnant gland. A substantial fraction of the differentially expressed genes was down-regulated, many of which are known to be elevated by prostaglandin F2A (PGF2A). In vitro , IFNT was found to mimic changes observed in the luteal transcriptome of early pregnancy. Key luteolytic genes such as endothelin-1 (EDN1), transforming growth factor-B1 (TGFB1), thrombospondins (THBSs) 1&2 and serpine-1 (SERPINE1) were downregulated in luteal en-dothelial cells. Luteal steroidogenic large cells (LGCs) were also found to be a target for the antilutelotytic actions of IFNT. IFNT-treated LGCs showed a significant reduction in the expression of the proapoptotic, antiangiogenic THBS1&2, as well as TGFBR1 and 2. Further-more, IFNT was shown to be a potent survival factor for luteal cells in vivo and in vitro , acti-vating diverse pathways to promote cell survival while suppressing cell death signals. Pen-traxin 3 (PTX3), robustly upregulated by IFNT in various luteal cell types, mediated many of the prosurvival effects of IFNT in LGCs. A novel reciprocal inhibitory crosstalk between PTX3 and THBS1 lends further support to their respective survival and apoptotic actions in the CL. Even though IFNT did not directly regulate progesterone synthesis, it could maintain its concentrations, by increasing luteal cell survival and by supporting vascular stabiliza-tion. The direct effects of IFNT in the CL, enhancing cell survival and vasculature stabiliza-tion while curbing luteolytic activities, may constitute an important complementary branch leading to the extension of the luteal lifespan during early pregnancy. (c) 2021 Elsevier Inc. All rights reserved.