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The latter includes key transcription factors that can instigate cellular reprogramming and transdifferentiation [ 18 , 19 , 20 , 21 , 22 ], which is largely seen as a promising therapeutic strategy in disease modeling [ 5 , 23 , 24 , 25 , 26 ].

In the following section, we review the role of diverse factors involved in cellular transdifferentiation towards regulating the cell fate in disease modeling. An increasing therapeutic focus in neural and cardiac research prompted a series of investigations in the area and led to significant progress being made in the field of in vitro and in vivo transdifferentiation. Multiple studies produced transdifferentiated cells that phenotypically resemble their natural counterparts and maintain prolonged functionality within the neural and cardiac tissues Table 1.

By instigating in vivo transdifferentiation in the brain of an adult mouse, a report in first demonstrated a proof-of-principle of the mechanism. In this report, Torper and colleagues enrolled both resident cells, i. The adopted transgenic and transplantation approach comprehensively demonstrated ease at yielding specialized populations, including dopaminergic, and DA neurons.

They suggested the suitability of astrocytes for neuron transdifferentiation considering their enriched and ubiquitous presence in the brain [ 27 ] Figure 2. Schematic diagram showing processes of cardiac and neuronal transdifferentiation from a normal somatic cell. Both processes highlight translational and regenerative potential of transdifferentiation in disease modeling and drug discovery. In another report, Niu et al. Of note, they found that a single TF- Sox2 was sufficient to transdifferentiate the target cells.

Importantly, this strategy produced proliferative precursor cells, such as native neuroblasts, and called them induced adult neuroblasts iANBs. Such iANBs—derived mature neurons were found to be associated with different subtypes yet mainly expressed calretinin [ 29 ]. They later carried out Sox2 -mediated transdifferentiation of astrocytes to neuroblasts in spinal cord injury in another report [ 30 ].

In the case of spinal cord injury, the GFAP-lentiviral delivery system was seen to improve astrocyte proliferation in the region and to form a glial scar, yet it was later found to restrict axon regeneration [ 31 ]. Additionally, iANB-derived GABAergic neurons were seen to form synapses with the native neuronal networks; however, their electrophysiological function could not be confirmed.

Moreover, the extent of viral load as a vector was suggested to be disadvantageous for transdifferentiation efficiency, and the survival of transduced cells was also found to be a limitation towards scaling its utility for disease modeling Table 1. These mature neurons were locally integrated into the neural circuits and sustained survival for about 2 months [ 32 ].

It was promising to see that NeuroD1 has the potential to transdifferentiate astrocytes into the glutamatergic neurons in the human in vitro model; however, no data on behavioral rehabilitation were captured.

Moreover, the post-mitotic status of neurons makes it tougher to systematically acquire transdifferentiation in target cells. Rouaux and Arlotta, by taking Fefz2 , i. They affirmed that a significant population of transdifferentiated cells retained these changes for about 4 weeks. Simultaneously, another report demonstrated similar results. In this report, De la Rossa and colleagues introduced Fefz2 in the brain cortex, yet they used the iontoporation and CreERT2 methods to stimulate the TF expression at different developmental stages [ 34 ].

Using specific promoters, they controlled TF expression in specific populations and effectively transdifferentiated L4 spiny neurons into L5B neurons that exhibited native phenotype, transcriptomic signature, axon character, and bidirectional signal connectivity Table 1.

Recently, Qin et al. In another recent report, Song et al. Although these studies still do not qualify directly for therapeutic applications or diseases modeling, they do demonstrate proof-of-principal that neurons with post-mitotic state can be transdifferentiated, and cell-to-cell conversion can be programmed. Given the clinical prevalence and translational significance of cardiovascular disease [ 44 ], the scope of somatic cell transdifferentiation to cardiomyocytes CMs has been widely investigated.

In one of the earliest reports, the researchers tried to revive an injured rat heart by instigating MyoD-mediated transdifferentiation of the heart fibroblasts into skeletal muscle cells [ 8 ]. Although the study involved the transfection of MyoD-expressing cells and embryonic-MHC, no data on the cell fusion or maturation embryonic myofibroblasts into functional cells and their integration with native cardiomyocytes were obtained.

However, the presence of myofiber like cells in the cardiac microenvironment hinted at an incomplete maturation of the cells into a skeletal muscle phenotype. Furthermore, an elicited immune response against the adenoviral vector that was used in high-dose in the study was suggested to compromise the outcome Figure 2.

This earliest report in many ways advanced the field by providing initial experimental knowledge and by facilitating further attempts that enrolled multiple TFs that aimed to regenerate and obtain mature CMs. Consistent with this, two independent reports in adopted a similar strategy and endeavored to regenerate the myocardium post-myocardial infarction MI by transdifferentiating the heart fibroblasts into induced-CMs iCMs in mouse heart.

Qian and colleagues further validated the fibroblastic origin of iCMs, and the transdifferentiated cells shared similar features to native cells in terms of morphology, transcriptome, sarcomeric design, and electrical behavior. The iCMs acquired identical electrical stimulation function to ventricular CMs and significantly improved cardiac function, while no arrhythmias or cardiac death events were reported.

This was even more evident in the investigation by Inagawa et al. Christoforou and colleagues further showed that expression of Myocd and Srf —by itself or in combination with Smarcd3 and Mesp1 —can enhance the basal yet needed cardio-inducing impact of the known TFs viz.

Gatat4, Ata4, Tbx5, and Mef2c during direct cellular reprogramming [ 45 ]. Of note, enriched expression of cardiac-specific genes, activated myocardial and physiology-related pathways, and decreased levels of fibroblastic markers were evidently seen in these reprogrammed iCM-like cells [ 46 ]. These reports emphasized the role of the native microenvironment in achieving functionally mature transdifferentiated cells, which could enable the revival of injured tissue.

Adopting a similar strategy and an additional TF- Hand2 , Song et al. This strategy indeed improved the iCM generation efficiency to 6. Moreover, another study also endeavored to achieve cell transdifferentiation after MI; however, it adopted a lentiviral approach including a cocktail of four micro-RNAs viz.

Another report from this group revealed that the electrical features of transdifferentiated iCMs subsets were comparable to the endogenous CMs, which was reflected in the moderately improved cardiac function [ 40 ].

However, a lesser efficiency of transdifferentiation and immature iCMs hinted at the limitations of the adopted strategy and stressed the need for process optimization. Further, Mathison et al. These cells were found to improve cardiac function in the post-infarct rat hearts. These reports demonstrated effective transdifferentiation as affirmed by lineage tracing or adopted co-transduction strategies, and by validation of iCMs fibroblastic origin.

However, it was believed that transdifferentiation efficiency could be improved further if this step were delayed after injury, as it could allow more fibroblasts migration to the infarct site [ 8 ] Table 1.

Cheng et al. These ciNPC exhibited multipotent phenotypes and efficiently differentiated into different neural cell types in both in vitro and in vivo systems Figure 2. Similarly, using a cocktail of nine small molecules M9 , Zhang et al. On top of these three molecules, the other small molecules were assessed. Of note, Hh-Ag 1. Interestingly, three chemicals, viz. They also highlighted the role of the Elk1 and Gli2 transcription factors, which function in MP-induced signaling and activate key neural genes that have specialized functions in determining the neural identity.

Cortes-Medina et al. Using the full-chemical strategy, in , two simultaneous reports successfully produced human and mouse neurons from their fibroblast cells [ 52 , 53 ]. Using Ascl1 , i. Of note, a cocktail of four molecules was found to efficiently stimulate neuronal transdifferentiation and it was evident without Ascl1.

They also identified an additional small molecule viz. On the mechanistic side, they elucidated that I-BET, a BET family bromodomain inhibitor essentially suppresses fibroblast-specific genes, whereas ISX9, a neurogenesis inducer, activates neuron-specific transcriptional program [ 52 ].

In another report, Hu et al. Consistent with this, they found that Forskolin with VCR can partially induce a neural transdifferentiation activity in the human fibroblast. Although the cocktail of above seven small molecules demonstrated a distinct transdifferentiation efficiency, the survival and maturation of the produced neurons remained largely compromised.

It led them to enroll extra neurotropic factors viz. This method was further employed to produce functional neurons from familial AD patients. In another report, Zhang et al. Extensive screening eventually led them to identify a cocktail of nine small molecules viz. Of note, these transdifferentiated neurons sustained survival for about five months in vitro and constituted multiple functionally viable synaptic networks Table 2 and Table 3.

Obtaining human cells and stem cells is a practical impediment. Given the non-invasive source of multiple types of cells, urine can be obtained from patients of any age. Urine cell-derived competent cells have emerged as a major tool for research given its therapeutic importance [ 55 ]. Xu et al. The transdifferentiated neurons exhibited a mature neuronlike phenotype and molecular signature as validated by the expression of neuronal markers. Further, Qin et al.

Although these reports showed efficient neuronal transdifferentiation from various cell types, the underlying molecular mechanism of these processes warrants further investigation.

However, this handful of reports represented preliminary results, and the authenticity of the transdifferentiated cells warranted further careful investigations. Later, Fomina-Yadlin et al. Katsuda et al. A, Y, and CHIR, could yield bipotent liver progenitor cells from mature hepatocytes. Of note, in vitro these liver progenitor cells can differentiate into biliary epithelial cells and active hepatocytes that can revive injured liver tissues in vivo.

In another report, Wang et al. Bay-K, RG, Bix, and SB, with tissue-specific mesenchymal feeders can facilitate transdifferentiation of human gastric epithelial cells to multipotent endodermal progenitor cells. These cells can further be systematically differentiated into hepatocytes, intestinal epithelial cells, and pancreatic endocrine cells [ 60 ].

Replicating a similar strategy, human iPSCs were subsequently produced that revolutionized the field of regenerative medicine [ 62 , 63 ]. In a significant report, Cheng et al. The cellular reprogramming capabilities of both sets of TFs and chemical models reflected their immense clinical utility in disease modeling [ 63 , 65 , 66 , 67 ] Figure 2. Cellular reprogramming refers to a group of approaches that allow researchers to halt or reverse the development of adult cells.

The validation of cellular reprogramming in human cells has paved the way for a slew of new stem cell biology, disease modeling, drug development, and regenerative medicine applications [ 19 ]. The presence of pluripotent stem cells in a population that gives rise to all cells is one of the most defining elements of early mammalian development [ 68 ]. Due to a shortage of primary cells from the human central nervous system CNS and peripheral nervous system, human-induced pluripotent stem cells hiPSCs can also be studied for neurogenerative disease [ 69 ].

However, researchers have been able to conduct studies on the recapitulation of physiological and pathological pathways in patient-derived lines.

This has resulted in more realistic disease modeling platforms [ 70 ]. These are widely utilized in drug discovery and safety investigations, for instance in the development of AD drugs with the goal of identifying chemicals that can inhibit or lower amyloid-beta levels [ 71 ] Table 3 and Table 4. TFs-induced cellular reprogramming and functional outcomes in neuronal and cardiac model systems.

Heart failure is another common illness that is linked to a high rate of morbidity and mortality. Coronary artery disease, genetic changes and mutations, viral infections, unfavorable immunological responses, and cardiac toxicity are the underlying causes [ 44 ]. This is due, in part, to roadblocks in translating research into treatment techniques.

Drug repositioning using disease modeling systems based on hiPSCs could be a vital process that draws on prior toxicological and safety investigations to uncover new applications for existing medications [ 72 ].

The components of the reprogramming cocktail, as well as the administration method, have undergone significant changes throughout time to improve efficiency and offer a safer product. The current problems that stymie the clinical utility of cellular reprogramming and its applications in biomedical research [ 65 ], drug discovery, and predictive safety pharmacology are the explicit topics covered in this review Figure 3.

In , a study reported full chemical-induced fibroblast to cardiomyocytes reprogramming for the first time. In this report, Fu et al. In the course of this, they observed the spontaneous formation of contractile patterns in the cells, and their clusters that were phenotypically similar to cardiomyocytes.

Such a phenotype was evident days post-treatment with the CRFVPT cocktail, which was quicker than an earlier published work that exhibited the emergence of the CiPSCs phenotype in 20 days [ 73 ]. They systematically performed the transdifferentiation using a two-stage strategy wherein the CRFVPT cocktail was utilized to instigate the induction in first stage and cardiomyocytes-supporting medium, with CHIR, PD, LIF, and insulin supplements, was used in the second stage. With this two-stage strategy, the CRFV regime was found to potently stimulate cardiac transdifferentiation to CiCMs that appeared to progress through a progenitor stage [ 73 ].

Cao et al. Additionally, in an extended screening, they found that two small molecules, viz. In a recent report, Singh et al. The combinatorial approach was suggested to enhance the generation and induction of cardiomyocytes and offered an improvement of the cardiac regeneration practice for disease modeling Table 3.

Embryonic development starts with a single cell, the zygote, and progresses through the steps of establishing diverse cell lineages, eventually assimilating cells into the embryonic structure. Smith and colleagues firstly evaluated the osteogenic differentiation of mouse embryonic stem cells ESCs in vitro after their collection from mice mESCs [ 78 ]. However, the conditions necessary to sustain pluripotency and self-renewal of mESCs and hESCs in vitro are quite different.

Therefore, adult somatic cell-derived induced pluripotent stem cells iPSCs are rapidly being examined as a less controversial patient-specific alternative to hESCs. Importantly, iPSCs and ESCs have a high degree of similarity, providing new promise for the use of pluripotent stem cells for regenerative therapies with fewer ethical problems and potentially improved patient specificity [ 65 ] Table 3.

The development of innovative stem cell-based models to investigate the underlying processes of lineage differentiation and embryonic morphogenesis has been aided by the availability of embryo-derived stem cells that capture the lineage propensity [ 80 ]. Reprogramming the adult somatic cells into induced pluripotent stem cells iPSCs is another effective model that has a bright future as regenerative medicine. Therefore, disease models are critical for revealing the molecular basis of a variety of diseases, enabling the development of new treatments.

Although the discovery of pluripotent transcription factors, including OSKM, were sufficient to efficiently transform mouse fibroblast cells into iPSCs [ 99 ], there are several drawbacks to existing iPSC technology, including the limited efficiency and a lengthy reprogramming process.

Therefore, in molecular neurobiology, the direct reprogramming of somatic cells to distinct subtypes of induced neurons iN shows a lot of promise [ ]. Certain transcription factor combinations are now known to directly create iN from a variety of cell types, which could be beneficial in the development of neurological illness models. This latest research is just the beginning of advancements that could allow us to use iN for disease modeling and medication in neurodegenerative diseases.

The new generation of iN is crucial for understanding disease mechanisms and developing medications to treat neurodegenerative diseases Table 4. Human pluripotent stem cells hPSCs are also an extremely useful model system for studying the genetic basis of human cardiovascular disorders [ 67 ]. Unlike nonhuman animal models, human pluripotent stem cells hPSCs can be closely genetically matched to patients [ ]. Human embryonic stem cells hESCs , first discovered in , can be produced directly from human embryos.

However, obtaining an hESC line often necessitates the destruction of an embryo that is unrelated to any live person [ 80 ]. As a result, induced pluripotent stem cells iPSCs are now the most important studies in which many types of human somatic cells have been effectively reprogrammed. One important goal related to patient-specific iPSCs will be to use or to create a cardiac-based model system that incorporates all the genetic loci involved in the pharmaceutical response [ ] Table 3.

Clinically significant mutations can be extracted from the cells of patients suffering from a specific genetic disorder. These patients were more susceptible to catecholamine-induced tachyarrhythmia that was reduced by beta-blockade therapy [ ]. These findings show that iPSCs may reliably recreate aberrant cellular phenotypes and behaviors in vitro, offering vital mechanistic insights into the disease process.

It will be extremely valuable not only for disease modeling research Table 1 but also for prospective clinical applications and high-content, large-scale drug screening methods Table 3 and Table 4. Pluripotent stem cells PSCs , which include embryonic stem cells ESCs and induced pluripotent stem cells iPSCs , have a limitless ability to self-renew and proliferate. This feature allows them to generate a therapeutically relevant number of cells for regenerative therapy [ 24 ].

This would help the researchers to better understand the mechanisms driving a variety of human genetic, malignant, and nonmalignant disorders. Genome editing techniques have also been utilized to fix disease-specific iPSC mutations, resulting in gene-corrected iPSCs that can be employed for autologous cell-based treatment [ ].

The number and kind of cells, their efficiency, footprint, and long-term translational goal influences all its reprogramming approaches. However, fibroblasts and peripheral blood mononuclear cells remain the gold standard, despite the usage of diverse cell types.

When compared to iPSCs produced from other parental tissues, blood cells were less likely to develop aberrant DNA methylation, and these cells exhibited stronger hematopoietic differentiation ability [ , ]. Therefore, the generation of patient-specific iPSCs provides a safer alternative for clinical applications. Transgenic animal models have traditionally been used to investigate disease pathogenesis but due to inherent variations across species, many of these models do not completely recreate illness characteristics [ ].

As a result, most research has depended on the investigation of disease pathology using peripheral blood cells, which have a short lifespan in culture [ ]. Genetic alterations, which are key tools for studying candidate gene function, are also hampered by the lack of a strategy to maintain and amplify the primary cells. The introduction of iPSC technology has revolutionized how we investigate reprogramming models and their derivatives for illuminating pathogenic events during disease start and progression.

It would otherwise go undetected in primary cells [ ]. Furthermore, in neuronal disorders, essential steps in generating and converting stem cell therapies from the bench to patients include identification of the proper stem cell type and understanding the mechanism of support [ 88 ].

There is substantial evidence that stem cell therapy can improve neurogenesis in patients with neurological diseases [ ]. Cell line-based chemical screening and animal testing have been used to develop a huge number of medications currently on the market [ ]. However, numerous medications failed to reach the market due to unanticipated side effects in late-stage trials, primarily cardiotoxicity and hepatotoxicity.

High-throughput screening assays against a library of hundreds of thousands of chemicals are possible because of a wide panel of disease-specific iPSCs and their derivatives [ ]. This method may make it easier to design new treatments. Disease modeling is a crucial technique for elucidating the molecular basis of a variety of diseases and enabling the development of new targeted therapeutics.

Despite advancements in iPSC technology, the absence of efficient induction techniques continues to limit the creation of these cells [ 24 ]. The present cellular reprogramming methods highlight the need for better stem cell production procedures. As a result, one of the ways that researchers developed was DeepNEU, a revolutionary unsupervised deep-machine learning framework for simulating iPSCs and enabling effective cellular reprogramming [ ].

It was confirmed by creating computer simulations of three iPSC models that had previously been produced experimentally and published in peer-reviewed journals.

The use of this computer technology to generate disease-specific artificially induced pluripotent stem cells aiPSCs has the potential to improve: 1 disease modeling; 2 rapid prototyping of wet-lab experiments; 3 grant application writing; and 4 specific biomarker identification, all at a low cost. This potential new technique is still being developed and validated, with the present focus on modeling rare genetic illnesses [ 65 , ].

This shows that in the near future transdifferentiation and reprogramming therapies are expected to be successfully put into clinical practice. A disease model represents the abnormal state of cells that occur in a specific disease. Therefore, it allows researchers to investigate and understand the intricate mechanisms that lead to the onset and further progression of the disease. These models can further be explored for developing and testing therapeutics. Cellular reprogramming of stem cells to create disease-in-a-dish models has gained a lot of attention over the past few years.

These disease models are capable of self-renewal and also differentiate into desired cellular types to capture the disease pathogenesis [ ] Figure 3. It was the use of ESCs derived from affected embryos that gave insights into the early developmental events of Fragile X Syndrome FXS , the most common genetic cause of autism.

It was found for the first time that FMR1 silencing of the mutated gene in an X-linked dominant manner happens only after differentiation and not in the embryonic stage [ ]. Using iPSCs, one of the earliest disease models developed was to study spinal muscular atrophy. The motor neurons produced by diseased iPSCs carried the histological markers of the disease and degenerated at a rate faster than the wildtype control neurons [ ].

A disease model for schizophrenia established using iPSCs derived from patients with a 4 bp deletion in the DISC1 locus has also been reported. This is one of the successful examples where the episomal vector approach was used for the generation of adult patient-derived iPSCs without the risk of insertional mutagenesis [ ]. All these models have been discussed in detail in another report [ ].

Organ-on-chip technology is another area showing progression at an accelerated rate. A group of researchers has generated a blood—brain barrier chip by integrating iPSCs and organ-on-chip technologies.

These chips can serve good as a disease model for CNS drug penetrability predictions [ ]. Another example is of a four-organ-chip consisting of interconnected miniaturized human intestine, liver, brain, and kidney equivalents created using pre-differentiated iPSCs. Three out of four models intestine, liver, and neuronal were shown to maintain defined marker expression under specific conditions for over 14 days; however, the renal model could not succeed as expected [ ].

Nonetheless, these efforts expedite new avenues for modeling microphysiological systems. These systems can effectively be used as autologous coculture crosstalk assays, understanding the disease mechanisms, and for further using the platform for drug testing. Along with providing mechanistic insights, these disease models have also been successfully employed to screen therapeutics.

Many drug candidates that appear to be effective and safe in preclinical cellular and animal models often fail when tested in human beings. This can be attributed to the non-reliability of the preclinical models in practice. These models fail to recapitulate human physiology to its best.

However, these cells do not reflect some of the important characteristics of human cardiomyocytes and also lack the expression of ion channels other than hERG. This often leads to incorrect assessments of drug effects. For instance, the action of Alfuzosin is mediated through sodium channels rather than hERG and causes QT prolongation.

So, it appears to be non-toxic when tested in hERG-overexpressing cell lines [ ]; however, testing in iPSC-CMs, it was identified as toxic [ ]. This example thus clearly demonstrates the importance of correct screening models. These genes encode voltage-gated potassium channels. The disease model for this syndrome, generated from iPSC-derived cardiomyocytes, showed significantly longer action potentials in comparison to the control cells.

The dominant-negative trafficking effect of KCNQ1 and the resulting reduction in rectifier current was also studied through this model. A study reported the use of neural stem cells differentiated from FXS patient-derived iPSCs in a well plate format high-throughput screening. Out of tested compounds, the authors were able to identify six compounds that modestly increased FMR1 gene expression in the patient-derived cells.

Though the results did not provide any clue on their clinical application the study still proves the principle in question [ ]. Next, iPSC-CMs have been reported to be employed for the screening of different drugs at 6 different concentrations for the cardiotoxicity test [ ]. Another similar study evaluated 51 previously characterized compounds in iPSC-CMs to study their effects on cardiomyocyte contraction [ ].

Further, a liposomal formulation of doxorubicin was also tested in a similar model. Doxorubicin in this new formulation was unable to penetrate cardiomyocytes, thereby approving its entry into phase I clinical trials [ ]. The concept of regenerative medicine involves the switching of stem cells or dedifferentiating somatic cells into stem cell-like multipotent cells.

These cells can proliferate and then re-differentiate into the desired lineage to repopulate the damaged or degenerated tissue with functional cells. The reprogramming of the cells can be conducted in vitro, in vivo, or ex vivo to regain their regenerative properties. The use of a single transcription factor, such as FOXN1, has been shown to regenerate the thymus in aged mice.

Though a lot of efforts are being made to explore and understand mammalian stem cell biology, the knowledge regarding the regenerative capacity of the mammalian system is still limited. However, it is known that the cellular environment, including the modulators present in the extracellular matrix, cytokines, and growth factors, plays a crucial role in this process [ ] Figure 3. There are plenty of examples that demonstrate the immense potential of regenerative medicine.

The first clinical trials using stem cell-derived products for treating neurological diseases in human were initiated by Geron in The system used hESCs-derived oligodendrocytes to remyelinate denuded axons in patients with thoracic level spinal injury. However, the study faced preclosure due to financial concerns [ ]. In a more recent study, intervertebral disc-derived iPSCs differentiated into neural precursor cells were transplanted into mice to investigate the effect on spinal injury. The precursor cells were observed to differentiate into early and matured neurons, significantly improving the hindlimb dysfunction in the injured mice [ ].

Sundberg et al. These cells were further seen to produce insulin when transplanted into diabetic mice, thereby normalizing hyperglycemic conditions and paving way for treating diabetes [ ]. The potential utility and feasibility of ESC or iPSC-derived cardiomyocyte transplantation therapy for myocardial regeneration have also been discussed in many reports. It has been shown that embryonic-stem-cell-derived cardiomyocytes, when transplanted into a guinea-pig model with an injured heart, protected it against arrhythmias.

The grafted muscles were also able to contract synchronously with the host muscle, improving the mechanical function of the injured heart and reducing the risk of ventricular tachycardia [ ]. Though many other successful reports have come to light, we are discussing only a few to emphasize the clinical applications of this approach. An alternative to the natural regenerative potential of mammalian stem cells is to induce transdifferentiation in somatic cells.

Differentiated cells, such as neurons derived from iPSCs, have been observed to represent an embryolike stage. The epigenetic changes that a cell undergoes as it ages or becomes diseased are therefore not reflected by the matured cells. This results in the importance of the transdifferentiation process, whereby the phenotype of one somatic cell type can be converted into another without an intermediate progenitor stage [ 73 ]. For instance, Ieda and his colleagues used a combination of Gata4, Mef2c, and Tbx5 developmental transcription factors to transdifferentiate postnatal cardiac or dermal fibroblasts into cardiomyocytelike cells.

The gene expression profile and function of the differentiated cells was also found to be similar to the adult cardiomyocytes [ ]. Similar studies enhancing the in vivo efficiency of cardiac cell reprogramming [ ] and the use of small molecules for the same have also been reported [ 74 ]. Based on 77 reviews. Highlights Dazzling: Vibrant colours intensify all eye make-up.

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