Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblasts are the most ubiquitous cells in complex organisms. They are the main cells of stromal tissue and play an important role in repair and healing of damaged organs. Here we report new data-initially serendipitous findings-that fibroblast-derived cell line (human fetal lung derived cells, MRC-5) have the morphology, growth rate and gene expression pattern characteristic of embryonic stem cells and cells of neuro-ectodermal origin. We have developed a serum-free culture system to maintain these cells in proliferative state. We discovered that, at proliferative state, these cells express transcription factors of pluripotent cells, OCT-3/4 and REX-1, and embryonic cell surface antigens SSEA-1, SSEA-3, and SSEA-4, as well as TRA-1-60 and TRA-1-81. In addition to embryonic cell markers, the fibroblasts expressed neuroectodermal genes: Musashi-1, nestin, medium neurofilament, and beta-III tubulin. RT-PCR data revealed that mesencephalic transcription factors, Nurr-1 and PTX-3, were also expressed in MRC-5 cells, and that these cells could be induced to express tyrosine hydroxylase (TH). Expression of TH followed down-regulation of genes associated with cell proliferation, OCT-3/4, REX-1, and beta-catenin. These data indicate that the cells commonly known as fibroblasts have some of the characteristics of stem cells, and can be induced to become neuroectodermal cells and perhaps even mature neurons.
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PMID:Human fibroblast-derived cell lines have characteristics of embryonic stem cells and cells of neuro-ectodermal origin. 1635 91

The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter life span compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties, including the development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers. In addition, expression of key pluripotency genes (ZFP42, PODXL, DNMT3B, C-MYC, LIN28, KLF4, NANOG, SOX2, and OCT4) was observed. We then tested the neural differentiation capacity and gene expression profiles of Cj-iPSCs and a marmoset embryonic stem cell line (Cj-ESC) after dual-SMAD inhibition. Exposure to CHIR99021 and sonic hedgehog (SHH) for 12 and 16 days, respectively, patterned the cells toward a ventralized midbrain dopaminergic phenotype, confirmed by expression of FOXA2, OTX2, EN-1, and tyrosine hydroxylase. These results demonstrate that common marmoset stem cells will be able to serve as a platform for investigating regenerative medicine approaches targeting the dopaminergic system.
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PMID:Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts. 2863 9