Cellular Reprogramming

Tumor tissue comprises a highly complex network of diverse cell types. The tumor microenvironment (TME) can be mainly subdivided into cancer cells and stromal cell compartments, the latter include different types of immune cells, fibroblasts, endothelial cells, and pericytes. Tumor cells reprogram immune cells and other stromal cells in the TME to constrain their antitumor capacity by creating an immunosuppressive milieu and metabolism competition. Moreover, the reprogramming effect on immune cells is localized not only in the tumor but also at the systemic level...

A combination of a MEK/ERK-signaling inhibitor and three chromatin-remodeling molecules enhances generation of platelet-producing megakaryocytes in vitro , possibly through direct reprogramming.

Last June, the stem cell community came together to celebrate the 20th anniversary of the International Society for Stem Cell Research (ISSCR), one of the leading organizations in the field. The hybrid event mixed a varied program filled with plenary talks, concurrent track sessions, poster presentations, exhibit booths, and plenty of opportunities to enhance stem cell research through bonding between academia and industry. This report highlights the Plenary sessions, with the main topics discussed by each speaker...

Developmental biology has been revolutionized by two recent articles showing that synthetic mouse embryos derived from embryonic stem cells (ESCs) can be grown ex vivo and complete gastrulation up to the organogenesis stage. This is a remarkable achievement that had never been attained using stem cells before. Both studies used transcription factors to reprogram extraembryonic cells, which they combined with naive ESCs. Further culture of these aggregates using gas-exchange bioreactors allowed these aggregates to proceed through gastrulation and organogenesis, resembling E8...

Budding off from the broader developmental biology and stem cell research fields, cellular reprogramming is now established as a prominent discipline in its own right. Direct cell reprogramming is defined as the cell fate conversion of a somatic cell toward another identity without a pluripotent intermediate state. In addition to the opportunity for mechanistic dissection of lineage commitment in human cells, the field offer the promise of diverse applications such as for disease modeling, cell replacement therapy, regenerative medicine, and immunotherapy that have recently spurred innovation and out of the box thinking to unleash the potential of cellular plasticity...

In the last decade, direct reprogramming has emerged as a novel strategy to obtain mature and functional dopamine neurons from somatic cells. This approach could overcome issues linked to the use of human pluripotent stem cells such as ethical concerns and safety problems that can arise from the overgrowth of undifferentiated cells after transplantation. Several conversion methodologies have been developed to obtain induced DA neurons (iDANs) or induced DA neuron progenitors (iDPs). iDANs have also proved to successfully integrate in mice striatum, alleviating Parkinson's disease (PD) motor symptoms...

A major improvement in the generation of astrocytes directly from human fibroblasts will now facilitate the study of how aging impacts on astrocyte function and whether this contributes to neurodegenerative disorders.

The oocyte in vitro maturation (IVM) technique is important in animal husbandry, biomedicine, and human-assisted reproduction. However, the developmental potential of in vitro matured oocytes is usually lower than that of in vivo matured (IVVM) oocytes. Amphiregulin (AREG) is an EGF-like growth factor that plays critical roles in the maturation and development of mammalian oocytes. This study investigated the effects of AREG supplementation during pig oocyte IVM on the subsequent development of cloned embryos...

Mesenchymal stem cell is a potent tool for regenerative medicine against control of incurable diseases in human and animals. Diabetes mellitus is one such condition marked with the blood glucose is high due to lack of insulin (INS) hormone secreted by the pancreatic cells. Rare, but sporadic, cases of dysfunctional pancreatic cells in goat as well as the promises of stem cell therapy as an off-the-shelf medicine prompted us to explore the potential of adipose-derived goat mesenchymal stem cells (AD-MSCs) to transdifferentiate into pancreatic islet-like cells...

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The direct conversion of adult human skin fibroblasts (FBs) into induced neurons (iNs) represents a useful technology to generate donor-specific adult-like human neurons. Disease modeling studies rely on the consistently efficient conversion of relatively large cohorts of FBs. Despite the identification of several small molecular enhancers, high-yield protocols still demand addition of recombinant Noggin. To identify a replacement to circumvent the technical and economic challenges associated with Noggin, we assessed dynamic gene expression trajectories of transforming growth factor-β signaling during FB-to-iN conversion...

Mesenchymal stem cells (MSCs) exist in many tissues and can differentiate into cells of multiple lineages, such as adipocytes, osteoblasts, or chondrocytes. MSC administration has demonstrated therapeutic potential in various degenerative and inflammatory diseases ( e.g. , graft-vs.-host disease, multiple sclerosis, Crohn's disease, organ fibrosis, and diabetes mellitus [DM]). The mechanisms involved in the therapeutic effects of MSCs are multifaceted. Generally, implanted MSCs can migrate to sites of injury, where they establish an anti-inflammatory and regenerative microenvironment in damaged tissues...

One major goal of regenerative medicine is the production of pancreatic endocrine islets to treat insulin-dependent diabetic patients. Among the different methods developed to achieve this goal, a particularly promising approach is direct lineage reprogramming, in which non-β-cells are directly converted to glucose-responsive, insulin-secreting β-like cells. Efforts by different research groups have led to critical insights in the inducing factors necessary and types of somatic tissues suitable for direct conversion to β-like cells...

Mitochondrial diseases are a heterogeneous group of rare genetic disorders caused by mutations in nuclear or mitochondrial DNA (mtDNA). These diseases are frequently multisystemic, although mainly affect tissues that require large amounts of energy such as the brain. Mutations in mitochondrial transfer RNA (mt-tRNA) lead to defects in protein translation that may compromise some or all mtDNA-encoded proteins. Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS) syndrome is mainly caused by the m...

Reprogramming of human dermal fibroblasts (HDFs) into induced cardiomyocyte-like cells (iCMs) represents a promising strategy for human cardiac regeneration. Different cocktails of cardiac transcription factors can convert HDFs into iCMs, although with low efficiency and immature phenotype. Here, GATA4, MEF2C, TBX5, MESP1, and MYOCD (GMTMeMy for short) were used to reprogram HDFs by retrovirus infection. We found that the exogenous expression stoichiometry of GATA4 (GATA4 stoichiometry) significantly affected reprogramming efficiency...

The vimentin (encoded by VIM) is one of the 70 human intermediate filaments (IFs), building highly dynamic and cell-type-specific web networks in the cytoplasm. Vim-/- mice exhibit process defects associated with cell differentiation, which can have implications for understanding cancer and disease. This review showed recent reports from studies that unveiled vimentin intermediate filaments (VIFs) as an essential component of the cytoskeleton, followed by a description of vimentin's physiological functions and process reports in VIF signaling pathway and gene network studies...

Understanding the pathophysiology of CNS-associated neurological diseases has been hampered by the inaccessibility of patient brain tissue to perform live analyses at the molecular level. To this end, neural cells obtained by differentiation of patient-derived induced pluripotent stem cells (iPSCs) are considerably helpful, especially in the context of monogenic-based disorders. More recently, the use of direct reprogramming to convert somatic cells to neural cells has emerged as an alternative to iPSCs to generate neurons, astrocytes, and oligodendrocytes...

Different development stages of porcine embryos have different tolerance to low temperature. Therefore, we took the porcine embryos after parthenogenetic activation (PA) as the model, to explore the optimal development stage for vitrification during morula (D4), early blastocyst (D5), and expanded blastocyst (D6) after PA (D0). Embryos were observed with microscope and analyzed by different staining after cryo-recovery for 24 hours. The quality of embryos was damaged after vitrification, including embryonic nuclei, DNA, cytoskeleton, and organelles...

This study examined the relationship between the timing of the first cleavage and in vitro development of bovine somatic cell nuclear transfer (SCNT) embryos treated with trichostatin A (TSA). SCNT embryos were visually assessed at 22, 26, and 48 hours after activation. Each embryo with two or more distinct blastomeres was transferred into a microwell and cultured until day 7. Irrespective of TSA treatment, approximately half of the cleaved embryos were observed at 22 hours, and a significantly higher blastocyst formation rate was shown in the SCNT embryos cleaved at 22 hours than those cleaved at ≥26 hours...

Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has emerged as a potential treatment for ischemic stroke. Preconditioning with pharmacological agents before cell transplantation has been shown to increase the efficiency of cell therapy. In this study, trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the neuroprotective effect of BMSCs preconditioned with Tre on cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre...