A combination of induced pluripotent stem cell (iPSC) technology and methods of nucleotide sequence editing allows clarifying contribution of genetic variants to human disease development. In this study, an iPSC line (ICGi045-A) of a RASopathy patient carrying a variant of unknown significance, c.985G>A (p.Glu329Lys) in SOS1, was generated. The ICGi045-A line displayed iPSC properties—similar morphology, expression of pluripotent state markers (OCT4, NANOG, SOX2, TRA-1-60), capacity to give rise to derivatives of three germ layers during spontaneous differentiation, and retained normal karyotype (46,XX). This line can be used for generating isogenic iPSC lines to find out clinical significance of c.985G>A (p.Glu329Lys) variant in SOS1.
The photoperiod is an important ecological factor synchronizing the endogenous rhythms of growth and development of the Atlantic salmon Salmo salar L. The changes in the FA content of phospholipids (PL) and triacylglycerols (TAG) during the growth and development of Atlantic salmon juveniles (fingerlings, parrs, and smolts) at different lighting and feeding regimes in aquaculture of the southern region (North Ossetia, Alania) were studied. A high content of saturated fatty acids (SFA) and a consistently high content of polyunsaturated fatty acids (PUFA) in PL (more than 40% of the total FA) were detected. An increase in the content of PUFA in TAG both in the salmon liver and in muscles during development from fingerlings to smolts indicated the biochemical changes in the fish organism preparing for smoltification and the transition to living in sea water. Among PUFA, n-3 PUFA dominated, while the content of n-6 PUFA was no more than 5% both in PL and TAG of juvenile salmon. At the same time, among PUFA the content of eicosapentaenoic acid 20:5(n-3) (EPA) in the muscles of both parrs and smolts was higher than in the liver, where docosapentaenoic acid 22:5(n-3) (DPA) dominated. The results of quantitative and qualitative changes in the FA components of lipids in juvenile salmon depending on changes in the lighting and feeding regimes are important for understanding the mechanisms of ecological and biochemical adaptations that determine the early development of salmon and its transition to the smoltification.
The foxg1 gene has been described as one of the key regulators of early differentiation and development of the vertebrate forebrain and related sensory organs. In this article, the authors describe for the first time the presence of three foxg1 paralogs in lampreys, representatives of Agnatha, one of the most evolutionarily ancient branches of vertebrates. While maintaining several common features, an expression patterns of foxg1 paralogs in lampreys demonstrate elements of spatial subfunctionalization. An assessment of the estimated timing of duplication of foxg1 lamprey genes suggests that these genes could have appeared as a result of two rounds of whole-genome duplications at the early stages of vertebrate evolution.
Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disease caused by mutations in the ACVR1 gene for which there is currently no effective therapy. Therefore, obtaining iPSCs for further modeling and development of treatment methods, including gene therapy, can be very promising. The authors herein describe the generation of the induced pluripotent stem cell (iPSCs) line RCMGi014-A from urinary sediment cells of a patient with clinically expressed and genetically proven (ACVR1:c.6176G>A) FOP. These iPSCs proliferate in dense monolayer cell colonies, have a normal karyotype (46,XY), express pluripotency markers (OCT4, SOX2, TRA-1-60, SSEA-4), and show the ability to differentiate into three germ layers, which confirms their pluripotent status.
Adipose tissue is a special type of connective tissue that comprises stromal-vascular cells, committed preadipocytes, and mature adipocytes. Adipose tissue exhibits high plasticity and is capable of both rapid physiological expansion and reduction in response to dietary changes. Under normal conditions, an increase in adipose tissue volume occurs through hyperplasia, while tissue expansion in obesity results from hypertrophy of existing adipocytes. Adipose tissue cells not only store energy in the form of triglycerides but also secrete crucial adipokines, regulating the overall body metabolism. In metabolic syndrome and obesity, alterations affect not only adipose tissue morphology but also adipocyte renewal and differentiation as well as the hormonal and secretory functions. The fundamental mechanisms regulating cell renewal and differentiation in adipose tissue warrant detailed investigation to comprehend the metabolic processes in the entire organism, both under normal and pathological conditions. This review provides insights into the principal regulators governing the transcriptional program that controls adipogenesis, as well as the key signaling cascades that influence adipocyte differentiation.
Technology of generation of induced pluripotent stem cells followed by differentiation into relevant cell type allows obtaining cell models for studying various inherited human diseases. In the study, an induced pluripotent stem cell (iPSC) line (ICGi046-A) was generated as a result of reprogramming of mononuclear cells of a RASopathy patient carrying pathogenic c.775T>A (p.Ser259Thr) variant in RAF1 to the pluripotent state. The ICGi046-A line demonstrated morphology characteristic of human pluripotent cells, normal karyotype (46,XY), expression of pluripotency markers (OCT4, NANOG, SOX2, TRA-1-60), and capacity to give rise to derivatives of three germ layers during spontaneous differentiation. The iPSC line can be used for studying molecular mechanisms of RASopathies.
Cystic fibrosis (CF) is a hereditary disease that leads to impaired functioning of chloride channels in cells, and, as a result, to a decrease in the viscoelastic properties of the secretion of all exocrine glands. Cystic fibrosis is the result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes the CFTR protein. In this study, induced pluripotent stem cells (iPSCs) were obtained from the skin fibroblasts of a patient with a homozygous mutation F508del CFTR (NM_000492.3(CFTR):c.1521_1523del). This deletion is the most common for cystic fibrosis. The resulting iPSC line had a normal karyotype, retained the original genotype, and also demonstrated the presence of pluripotency markers (OCT4, SOX2, NANOG, SSEA4, TRA-1-60) and the ability to differentiate into derivatives of three germ layers.
The germes gene is a marker of germ plasm and primordial germ cells (PGC). It is described for the African clawed frog Xenopus laevis. Overexpression of its mutant form negatively affects the formation and migration of PGC. However, it was unknown until now how widely this gene is represented in animals of different phylogenetic groups. For this work, the authors performed bioinformatic analysis of genomic and transcriptome sequences of animals with germ plasm. We found out that the germes homologs are present only in representatives of the genera Xenopus and Hymenochirus of the family Pipidae (order Anura). The obtained results were confirmed by RT-PCR analysis of the expression of the germes orthologs in the ovaries of six representatives of different Anura families. Phylogenetic analysis of cloned sequences of the germes homologs suggests the appearance of this gene in the ancestors of Pipidae and its secondary loss in the genus Pseudohymenochirus. It is also shown that the amino acid sequences of the functional domains of the Germes protein are rather conservative.
—The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor and its target genes play a fundamental role in detoxification, regulation of developmental processes, maintenance of homeostasis, and in the occurrence of oncological and autoimmune diseases and drug metabolism. The high conservatism of vertebrate AHR allowed us to study its functions in vivo using transformed Drosophila melanogaster fruit flies with human or mouse AHR gene and compare the ectopic effect of their expression with the expression of spineless gene, Drosophila AHR homologue. This work demonstrates for the first time that vertebrate AHR exhibits its functional activity in Drosophila embryogenesis, in leg imaginal discs, and in somatic cells of the female reproductive system in the absence of exogenous ligands.
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