Stem Cells Applications in Therapeutics and Site-Specific Genome Editing Through CRISPR Cas9 System

Stem cells are immature cells that have ability to differentiate into all specific and mature cells in body. The two main characteristics of stem cells are selfrenewable and ability to differentiate into all mature, functional and adult cells types. There are the two major classes a) pluripotent stem cells which have potential to differentiate in all adult cell and b) multipotent stem cells which have capacity to differentiate into many adult cells but not in all cell types. Due to the self-renewable ability stem cells are used in therapeutics, tissue regeneration, disease modeling, regenerative medicines and to treat cardiovascular diseases, neural disorders such as Parkinson’s disease and most importantly to treat carcinomas. The human induced pluripotent stem cells provide a great platform to study and treatment of human diseases because these are able to differentiate into many functional and specialized adult cells of body. The genome editing tools such as CRISPR Cas9 system and TALENs are used to generate multiple DNA variants in hPSCs by inducing site specific mutations, frame shift mutation and deletion. In present days CRISPR Cas9 is more efficient and frequent method for genome editing which is derived from bacterial cell.

Stem Cells Applications in Therapeutics and Site-Specific Genome Editing Through CRISPR Cas9 System

Stem cells are immature cells that have ability to differentiate into all specific and mature cells in body. The two main characteristics of stem cells are self-renewable and ability to differentiate into all mature, functional and adult cells types. There are the two major classes a) pluripotent stem cells which have potential to differentiate in all adult cell and b) multipotent stem cells which have capacity to differentiate into many adult cells but not in all cell types.

Drosophila larval epidermal cells only exhibit epidermal aging when they persist to the adult stage

Holometabolous insects undergo a complete transformation of the body plan from the larval to the adult stage. In Drosophila, this transformation includes replacement of larval epidermal cells (LECs) by adult epidermal cells (AECs). AECs in Drosophila undergo a rapid and stereotyped aging program where they lose both cell membranes and nuclei. Whether LECs are capable of undergoing aging in a manner similar to AECs remains unknown. Here, we address this question in two ways. First, we looked for hallmarks of epidermal aging in larvae that have a greatly extended third instar and/or carry mutations that would cause premature epidermal aging at the adult stage. Such larvae, irrespective of genotype, did not show any of the signs of epidermal aging observed in the adult. Second, we developed a procedure to effect a heterochronic persistence of LECs into the adult epidermal sheet. Lineage tracing verified that presumptive LECs in the adult epidermis are not derived from imaginal epidermal histoblasts. LECs embedded within the adult epidermal sheet undergo clear signs of epidermal aging; they form multinucleate cells with each other and with the surrounding AECs. The incidence of adult cells with mixed AEC nuclei (small) and persistent LEC nuclei (large) increased with age. Our data reveals that epidermal aging in holometabolous Drosophila is a stage-specific phenomenon and that the capacity of LECs to respond to aging signals does exist.

Physiological and Aberrant γ-Globin Transcription During Development

The expression of the fetal Gγ- and Aγ-globin genes in normal development is confined to the fetal period, where two γ-globin chains assemble with two α-globin chains to form α2γ2 tetramers (HbF). HbF sustains oxygen delivery to tissues until birth, when β-globin replaces γ-globin, leading to the formation of α2β2 tetramers (HbA). However, in different benign and pathological conditions, HbF is expressed in adult cells, as it happens in the hereditary persistence of fetal hemoglobin, in anemias and in some leukemias. The molecular basis of γ-globin differential expression in the fetus and of its inappropriate activation in adult cells is largely unknown, although in recent years, a few transcription factors involved in this process have been identified. The recent discovery that fetal cells can persist to adulthood and contribute to disease raises the possibility that postnatal γ-globin expression could, in some cases, represent the signature of the fetal cellular origin.

A Genetic Model Reveals Biological Features of Neonatal CD4 Helper Cells Undergone Homeostasis in Mice

CD4+ T cells are essential for regulating effective immune response to pathogens and immune balance. Recent studies have demonstrated the unique features of T cells in neonate mice, such as more sensitive to antigen response and preference toward T helper 2 (Th2) response and regulatory T cells (Tregs) differentiation. However, the biological characteristics of neonatal age-derived CD4+ T cells following homeostasis remain unclear. Here we utilized a lineage tracing model of TCRδCreERR26ZsGreen to mark neonatal- and adult-derived CD4+ T cells followed by a combination analysis of activation, proliferation, survival, and differentiation. Our results showed that neonatal CD4+ T cells had higher capacity of activation, proliferation, apoptosis, and differentiation toward Th2 and T helper 17 (Th17) lineages, accompanied by a reduced potential for T helper 1 (Th1), T helper 9 (Th9), and Treg lineages. In contrast, tracked neonatal CD4+ T cells exhibited similar characters of above-mentioned of tracked adult cells in adult mice. Therefore, our data support a natural requirement for CD4+ T cells to acquire fully-equipped functional potentials of adult cells.

Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

RationaleYoung children (typically those <10 years old) are less susceptible to SARS-CoV-2 infection and symptoms compared to adults. However, the mechanisms that underlie these age-dependent differences remain to be determined and could inform future therapeutics for adults.ObjectiveTo contrast the infection dynamics of SARS-CoV-2 in primary nasal epithelial cells from adults and children.MethodsViral replication was quantified by plaque assay. The cellular transcriptome of infected and uninfected cells was assessed by RNA-seq. ACE2 and TMPRSS2 protein expression were quantified by Western Blot.Measurements and Main ResultsWe report significantly higher SARS-CoV-2 replication in adult compared to pediatric nasal epithelial cells. This was restricted to SARS-CoV-2 infection, as the same phenomenon was not observed with influenza virus infection. The differentiational SARS-CoV-2 replication dynamics were associated with an elevated type I and III interferon response, and a more pronounced inflammatory response in pediatric cells. No significant difference between the two age groups was observed in the protein levels of ACE2 and TMPRSS2.ConclusionsOur data suggest that the innate immune response of pediatric nasal epithelial cells, and not differential receptor expression, may contribute to the reported reduced SARS-COV-2 infection and symptoms reported amongst children.At a Glance CommentaryScientific Knowledge on the SubjectThere is now a growing body of evidence that children are less susceptible to SARS-CoV-2 infection compared to adults and if infected, children are more likely to develop an asymptomatic infection. The reasons for this remain unclear. In particular, the role of the pediatric nasal epithelium, the primary point of viral entry into the human host, in this differential susceptibility has yet to be investigated.What This Study Adds to the FieldOur study indicates that pediatric nasal epithelial cells produce a more vigorous anti-viral and pro-inflammatory response to SARS-CoV-2 compared to adult cells. This is associated with reduced SARS-CoV-2, but not influenza virus, replication in pediatric epithelial cells. We also show that on a protein level SARS-CoV-2 receptor expression on nasal epithelial cells is not significantly different between children and adults. These data provide an important insight into pediatric infections with SARS-CoV-2.

Stem Cells Applications in Therapeutics and Site-Specific Genome Editing Through CRISPR Cas9 System

Stem cells ae immature cells that have ability to differentiate into all specific and mature cells in body. The two main characteristics of stem cells are selfrenewable and ability to differentiate into all mature, functional and adult cells types. There are the two major classes a) pluripotent stem cells which have potential to differentiate in all adult cell and b) multipotent stem cells which have capacity to differentiate into many adult cells but not in all cell types. Due to the self-renewable ability stem cells are use in therapeutics, tissue regeneration, disease modeling and regenerative medicines and to treat cardiovascular diseases, neural disorders such as Parkinson’s disease and most importantly to treat carcinomas. The human induced pluripotent stem cells provide a great platform to study and treatment of human diseases because these are able to differentiate into many functional and specialized adult cells of body. The genome editing tools such as CRISPR Cas9 system and TALENs are used to generate multiple DNA variants in hPSCs by inducing site specific mutations, frame shift mutation and deletion. In present days CRISPR Cas9 is more efficient and frequent method for genome editing which is derived from bacterial cell.

Transdifferentiation In Neuroscience: Lights And Shadows

Adult cells are believed to maintain their differentiated status under stable homeostatic conditions, while cellular identity can become plastic when homeostasis is perturbed such as during an injury and inflammation [1]. Indeed, it is now evident that cell identity is more flexible and plastic than previously thought