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Examples Of In Vitro Transdifferentiation By Lineage-instructive Approach
A list of examples of transdifferentiation: *Mouse fibroblasts, chondroblasts, and pigmented retinal epithelial cells → myoblasts (MyoD) *Fibroblasts → melanocytes (MITF) *Glial cells → neurons (Pax6) *Erythorid-megakaryocytic cells → monocytic cells ( SPI1/PU.1) *B-cell progenitors → functional macrophages ( C/EBPα) *Rat hepatic cell line → insulin-producing cells (Pdx1 and Ngn3) *Fibroblasts → macrophage-like cells (PU.1 and C/EBPα or C/EBPβ) *Postnatal cardiac and dermal fibroblasts → cardiomyocytes (Gata4, myocyte enhancer factor 2C, and Tbx5) *Fibroblasts → heptaocyte-like cells (Gata4, Hnf1alpha, and Foxa3) or (Hnf4alpha and Foxa1, Foxa2 or Foxa3) *Fibroblasts → neurons (Ascl1, Pou3f2/Brn2, and Myt1l) *Human fibroblasts → neurons (Ascl1, Brn2, Mytl1, and NeuroD) or (miR-9/9-124, Neurod2, Ascl1, and Myt1l) *Human fibroblasts → functional neurons ( miR-124, Myt1l and Brn2) *Fibroblasts → dopaminergic neurons (Ascl1, Brn2, Myt1l, Lmx1a, and FoxA2) or ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transdifferentiation
Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine. The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in silk moths undergoing metamorphosis. Discovery Davis et al. 1987 reported the first instance (sight) of transdifferentiation where a cell changed from one adult cell type to another. Forcing mouse embryonic fibroblasts to express MyoD was found to be sufficient to turn those cells into myoblasts. Natural exa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GATA4
Transcription factor GATA-4 is a protein that in humans is encoded by the ''GATA4'' gene. Function This gene encodes a member of the GATA family of zinc finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function. Mutations in this gene have been associated with cardiac septal defects as well as reproductive defects. GATA4 is a critical transcription factor for proper mammalian cardiac development and essential for survival of the embryo. GATA4 works in combination with other essential cardiac transcription factors as well, such as Nkx2-5 and Tbx5. GATA4 is expressed in both embryo and adult cardiomyocytes where it functions as a transcriptional regulator for many cardiac genes, and also regulates hypertrophic growth of the heart. GATA4 promotes cardiac morphogenesis, cardiomyocytes survival, and m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Induced Stem Cells
Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent – iMSC, also called an induced multipotent progenitor cell – iMPC) or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells. Three techniques are widely recognized: * Transplantation of nuclei taken from somatic cells into an oocyte (egg cell) lacking its own nucleus (removed in lab) * Fusion of somatic cells with pluripotent stem cells and * Transformation of somatic cells into stem cells, using the genetic material encoding reprogramming protein factors, recombinant proteins; microRNA, a synthetic, self-replicating polycistronic RNA and low-molecular weight ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transdifferentiation
Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine. The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in silk moths undergoing metamorphosis. Discovery Davis et al. 1987 reported the first instance (sight) of transdifferentiation where a cell changed from one adult cell type to another. Forcing mouse embryonic fibroblasts to express MyoD was found to be sufficient to turn those cells into myoblasts. Natural exa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ASCL1
Achaete-scute homolog 1 is a protein that in humans is encoded by the ''ASCL1'' gene. Because it was discovered subsequent to studies on its homolog in Drosophila, the Achaete-scute complex, it was originally named MASH-1 for mammalian achaete scute homolog-1. Function This gene encodes a member of the basic helix-loop-helix (BHLH) family of transcription factors. The protein activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other BHLH proteins is required for efficient DNA binding. This protein plays a role in the neuronal commitment and differentiation and in the generation of olfactory and autonomic neurons. It is highly expressed in medullary thyroid cancer and small cell lung cancer and may be a useful marker for these cancers. The presence of a CAG repeat in the gene suggests that it may also play a role in tumor formation. Role in neuronal commitment Development of the vertebrate nervous system begins when the neural tube forms in the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mir-124 MicroRNA Precursor Family
The miR-124 microRNA precursor is a small non-coding RNA molecule that has been identified in fliesMI0000373, nematode wormsMI0000302, mouseMI0000150 and humanMI0000443. The mature ~21 nucleotide microRNAs are processed from hairpin precursor sequences by the Dicer enzyme, and in this case originates from the 3' arm. miR-124 has been found to be the most abundant microRNA expressed in neuronal cells. Experiments to alter expression of miR-124 in neural cells did not appear to affect differentiation. However these results are controversial since other reports have described a role for miR-124 during neuronal differentiation. Targets of miR-124 * Visvanathan ''et al.'' showed that miR-124 targets the mRNA of the anti-neural function protein SCP1 (small C-terminal domain phosphatase 1). * Makeyev et al. showed that miR-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in non-neuronal cells. *Arrant et al. wrote that m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FOXA2
Forkhead box protein A2 (FOXA2), also known as hepatocyte nuclear factor 3-beta (HNF-3B), is a transcription factor that plays an important role during development, in mature tissues and, when dysregulated or mutated, also in cancer. Structure FOXA2 belongs to a subfamily of the Forkhead box (FOX) transcription factors, the other members being FOXA1 and FOXA3. This subfamily of mammalian FOX proteins was first identified because of their ability to bind DNA in rat liver nuclear extracts. The proteins were therefore originally named hepatocyte nuclear factor 3 alpha, beta and gamma. These transcription factors contain a forkhead domain (also known as the winged-helix domain) flanked by sequences necessary for nuclear localization Their N- and C-termini are also conserved and serve as transactivation domains. Functions FOXA transcription factors have “pioneering” property, i.e. they can directly bind to condensed chromatin. This feature has been observed both ''in vitro'' a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FOXA1
Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the ''FOXA1'' gene. Function FOXA1 is a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin as a pioneer factor. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. Marker in breast cancer FOXA1 in breast cancer is highly correlated with ERα+, GATA3+, and PR+ protein expression as well as endocrine signaling. FOXA1 acts as a pioneer factor for ERa in ERα+ breast cancer, and its expression might identify ERα+ cancers that undergo rapid reprogramming of ERa signaling that is associated with poor outcomes and treatment resistance. Conversely, in ERα− breast cancer FOXA1 is highly correlated wit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FOXA3
Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) is a protein that in humans is encoded by the ''FOXA3'' gene. Function HNF-3G is a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important .... Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. References Further reading * * * * * * * * * * * * * * * * * * * External links * {{Transcription factors, g3 Forkhead transcription factors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TBX5 (gene)
T-box transcription factor TBX5, (T-box protein 5) is a protein that in humans is encoded by the ''TBX5'' gene. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. ''TBX5'' is located on the long arm of chromosome 12. ''TBX5'' produces a protein called T-box protein 5 that acts as a transcription factor. ''TBX5'' is involved with forelimb and heart development. This gene impacts the early development of the forelimb by triggering fibroblast growth factor, FGF10. Function ''TBX5'' is involved with the development of the four heart chambers, the electrical conducting system, and the septum separating the right and left sides of the heart. ''TBX5'' is a transcription factor that codes for the protein called ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neurogenins
Neurogenins are a family of bHLH transcription factors involved in specifying neuronal differentiation. It is one of many gene families related to the ''atonal'' gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1. In neural crest cells, the neurogenin family is essential for neurogenesis in the developing dorsal root ganglia and development of the sensory lineage. Neurogenin-1 Neurogenin 1 (Ngn1) is a Class-A bHLH, basic-helix-loop-helix (bHLH) transcription factor that acts as a regulator for neuronal cellular differentiation, differentiation, and acts by binding to enhancer (genetics), enhancer regulatory elements on genes that encode transcriptional regulators of neurogenesis. In order for Ngn1 to bind with high fidelity with genomic DNA, it must dimer (chemistry), dimerize with another bHLH protein. Ngn1 is a proneural gene because its expression is seen prior to neural lineage ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals. Structure Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli. Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibroblasts (called fibrocytes) are smaller, spindle-shaped, and have a reduced amount of rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters. Unlike the epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina components in so ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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