Search results for "Transdifferentiation"
showing 10 items of 21 documents
Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and De…
2016
Objective.Microvascular damage is pivotal in the pathogenesis of systemic sclerosis (SSc), preceding fibrosis, and whose trigger is not still fully understood. Perivascular progenitor cells, with profibrotic activity and function, are identified by the expression of the isoform 12 of ADAM (ADAM12) and this molecule may be upregulated by transforming growth factor-β (TGF-β). The goal of this work was to evaluate whether pericytes in the skin of patients with diffuse cutaneous SSc (dcSSc) expressed ADAM12, suggesting their potential contribution to the fibrotic process, and whether TGF-β might modulate this molecule.Methods.After ethical approval, mesenchymal stem cells (MSC) and fibroblasts …
Myeloid leukemia with transdifferentiation plasticity developing from T-cell progenitors
2016
Unfavorable patient survival coincides with lineage plasticity observed in human acute leukemias. These cases are assumed to arise from hematopoietic stem cells, which have stable multipotent differentiation potential. However, here we report that plasticity in leukemia can result from instable lineage identity states inherited from differentiating progenitor cells. Using mice with enhanced c-Myc expression, we show, at the single-cell level, that T-lymphoid progenitors retain broad malignant lineage potential with a high capacity to differentiate into myeloid leukemia. These T-cell-derived myeloid blasts retain expression of a defined set of T-cell transcription factors, creating a lymphoi…
Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression
2018
Growing evidence points to exosomes as key mediators of cell–cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated inter…
2017
AbstractThe development of a successful lineage reprogramming strategy of liver to pancreas holds promises for the treatment and potential cure of diabetes. The liver is an ideal tissue source for generating pancreatic cells, because of its close developmental origin with the pancreas and its regenerative ability. Yet, the molecular bases of hepatic and pancreatic cellular plasticity are still poorly understood. Here, we report that the TALE homeoprotein TGIF2 acts as a developmental regulator of the pancreas versus liver fate decision and is sufficient to elicit liver-to-pancreas fate conversion both ex vivo and in vivo. Hepatocytes expressing Tgif2 undergo extensive transcriptional remode…
Caracterización y mantenimiento in vitro de células germinales inducidas para la preservación de la fertilidad
2017
INTRODUCCIÓN La infertilidad es una condición clínica que afecta al 15% de las parejas en edad reproductiva; de las cuales un 28% se ven afectadas por diferentes patologías que resultan en la ausencia de gametos, dentro de este porcentaje se incluyen pacientes con fallo ovárico precoz, mujeres postmenopáusicas y pacientes masculinos diagnosticados de azoospermia no-obstructiva o cualquier otra patología que conlleve la ausencia de espermatozoides funcionales o, al menos, espermátidas elongadas que permitan su uso en tratamientos de reproducción asistida. Estas patologías producen infertilidad en el 1% de las mujeres y el 0.63% de los hombres, en la población general; como consecuencia el us…
Beyond islet trasplantation in diabetes cell terapy:from embryonic stem cells to transdifferentation of adult cells
2013
Exogenous insulin is, at the moment, the therapy of choice of diabetes, but does not allow tight regulation of glucose leading to long-term complications. Recently, pancreatic islet transplantation to reconstitute insulin-producing cells, has emerged as an alternative promising therapeutic approach. Unfortunately, the number of donor islets is too low compared with the high number of patients needing a transplantation leading to a search for renewable sources of high-quality -cells. This review, summarizes more recent promising approaches to the generation of new -cells from embryonic stem cells for transdifferentiation of adult cells, particularly a critical examination of the seminal work…
Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells
2006
AIM: To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS: BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequ…
Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes
2003
Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons1,2. Several groups have attributed this apparent plasticity to ‘transdifferentiation’3,4,5. Others, however, have suggested that cell fusion could explain these results6,7,8,9. Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resul…
Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex
2014
Summary The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX)+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following …
The art of forging neurons: direct reprogramming of somatic cells into induced neuronal cells
2013
Abstract Cellular reprogramming has shed new light on the plasticity of terminally differentiated cells and unearthed novel strategies for cell-based therapies to treat neurological disorders. With accumulating knowledge of the programs underlying the genesis of the distinct neural cell types, particularly the identification of crucial transcription factors and microRNAs, reprogramming of somatic cells of different origins into induced neuronal cells or neural stem cells has been successfully achieved. Starting with the general concept of reprogramming, we discuss three different paradigms: (1) direct conversion of central nervous system (CNS) foreign cells such as skin fibroblasts in…