Abstract: The present disclosure provides methods for generating and maintaining thymic cell in vitro. Compositions and systems of cell populations that include thymic cells are also provided herein. In one aspect, the disclosure provides a method for generating a population of thymic cells in vitro by culturing a population of cells in the presence of a soluble factor, a mineral or a combination thereof to induce differentiation or maturation of the population of cells to thymic cells; wherein the population of cells is optionally engineered to express a cell surface receptor or an intracellular factor; and wherein the population of cells comprises one or more cell types selected from the group consisting of pluripotent stem cells (PSCs), definitive endodermal (DE) cells, third pharyngeal pouch endodermal (PPE) cells, and anterior foregut endodermal (AFE) cells.

Abstract: The present invention relates generally to a therapeutic protocol for treating a subject having cancer. Taught herein is a method of treating cancer or reducing the risk of recurrence of cancer in a subject following an anti-cancer therapy.

Abstract: The present invention relates generally to a therapeutic protocol for treating a subject having cancer. Taught herein is a method of treating cancer or reducing the risk of recurrence of cancer in a subject following an anti-cancer therapy.

Abstract: The present specification relates generally to a therapeutic protocol for treating a subject having cancer. Taught herein is a method of treating cancer or reducing the risk of recurrence of cancer in a subject following an anti-cancer therapy.

Abstract: The present disclosure provides a method of generating mature mesenchymal stem cells and the cell culture medium used in such method. Also disclosed herein include a mesenchymal stem cell culture obtained by the method as disclosed herein, and uses thereof.

Abstract: The present invention relates to antisense oligonucleotides for modulating the activity of glycine decarboxylase (GLDC). In particular, the present invention relates to antisense oligonucleotides capable of inducing exon skipping of RNA. Also claimed are pharmaceutical compositions, kits and methods of treating cancer and inducing exon-skipping using said antisense oligonucleotides. In addition, a method for aiding the categorising or determining prognosis of a cancer or in selecting a therapeutic strategy for a patient with cancer, based on assessing the level of GLDC nucleic acid, protein or activity in a sample derived from the patient is provided.

Abstract: The present disclosure relates to a method of determining the presence of lung cancer in a subject comprising the steps of detecting an expression level of miR-1246 alone or in combination with an expression level of miR-1290 in a sample obtained from the subject wherein the increase in miR-1246 and/or miR-1290 in the sample obtained from the subject relative to the expression level of miR-1246 or miR-1290 in the control sample indicates the presence of lung cancer in the subject. The disclosure further comprises a method of monitoring a response to therapy in a lung cancer patient, a method of prognosis of lung cancer in a patient and a method for treating lung cancer in a subject comprising the use of inhibitors of miR-1246 and/or miR-1290 alone or in combination. In a specific embodiment, miR-1246 and/or miR-1290 levels are used to predict response to chemotherapy and progression in human non-small cell lung cancer (NSCLC) patients.

Abstract: The present specification relates generally to a therapeutic protocol for treating a subject having cancer. Taught herein is a method of treating cancer or reducing the risk of recurrence of cancer in a subject following an anti-cancer therapy.

Abstract: The present disclosure provides a method of generating mature mesenchymal stem cells (MSC) from lateral plate mesoderm comprising culturing the lateral plate mesoderm cells on an extracellular matrix in a MSC cell culture media comprising (i) fibroblast growth factor; (ii) platelet-derived growth factor (PDGF); (iii) epidermal growth factor (EGF) and (iv) ascorbic acid. Also claimed are MSCs obtained by said culture method and a method of treating cartilage and bone disease in a patient using said cells. In addition, a culture medium for deriving primitive streak mesendoderm cells from pluripotent stem cells comprising (a) activin; (b) WNT-signalling activator; and/or (c) fibroblast growth factor and a culture medium for deriving lateral plate mesoderm cells from primitive streak mesendoderm cells comprising (1) fibroblast growth factor; (2) bone morphogenetic protein; (3) follistatin; and optionally Rho-associated protein kinase (ROCK) inhibitor are claimed.

Abstract: The present invention relates to antisense oligonucleotides for modulating the activity of glycine decarboxylase (GLDC). In particular, the present invention relates to antisense oligonucleotides capable of inducing exon skipping of RNA. Also claimed are pharmaceutical compositions, kits and methods of treating cancer and inducing exon-skipping using said antisense oligonucleotides. In addition, a method for aiding the categorising or determining prognosis of a cancer or in selecting a therapeutic strategy for a patient with cancer, based on assessing the level of GLDC nucleic acid, protein or activity in a sample derived from the patient is provided.

Abstract: The present disclosure provides a method of directly converting a stem cell into a lineage specific cell, comprising the steps of a) transfecting a stem cell with at least one expression vector comprising i) one or more cell lineage reprogramming factors operably linked to an inducible promoter and ii) a selection marker; and b) inducing the transfected stem cell from stem a) with an inducing agent to directly convert said stem cell into a lineage-specific cell. Particularly exemplified are methods of transfecting a stem cell with SA-ASCL1 (phospho-mutant), DLX2, LHX6 and miR-9/9*-124 linked to a doxycycline inducible promoter to convert the stem cell into an inhibitory neuron and transfecting with NeuroD2 linked to a doxycycline inducible promoter to convert a stem cell into an excitatory neuron.

Abstract: The present disclosure provides methods and kits for the differentiation of stem cells into relevant liver cell lineages, as well as methods of using the relevant liver cell lineages in screening for a cellular response, a phenotype and in the treatment of a condition. In one embodiment, stem cells are first differentiated into cells of the definitive endoderm lineage, which are differentiated into posterior foregut (PFG) lineage cells by one or more of retinoic acid activators and/or one or more inhibitors of transforming growth factor-? (TGF?).

Abstract: Targeting metabolic enzymes in human cancer Abstract Lung cancer is a devastating disease and a major therapeutic burden with poor prognosis. The functional heterogeneity of lung cancer (different tumor formation ability in bulk of tumor) is highly related with clinical chemoresistance and relapse. Here we find that, glycine dehydrogenase (GLDC), one of the metabolic enzyme involved in glycine metabolism, is overexpressed in various subtypes of human lung cancer and possibly several other types of cancers. GLDC was found to be highly expressed in tumor-initiating subpopulation of human lung cancer cells compared with non-tumorigenic subpopulation. By array studies we showed that normal lung cells express low levels of GLDC compared to xenograft and primary tumor. Functional studies showed that RNAi inhibition of GLDC inhibits significantly the clonal growth of tumor-initiating cells in vitro and tumor formation in immunodeficient mice.

Abstract: The present disclosure provides an understanding of the regulation of the developmental phases of stem cells and their induction into relevant cell lineages, such as primitive streak, endoderm, mesoderm, or subterrotories of endoderm's. In particular, the present disclosure provides methods, culture medium and kits for the maintenance and differentiation of stem cells into relevant cell lineages.

Abstract: We provide for the use of Tbx3 (GenBank Accession Number: NM_005996.3 (SEQ ID NO. 1), NP_005987.3 (SEQ ID NO. 2), NM_016569.3 (SEQ ID NO. 3), NP_057653.3 (SEQ ID NO. 4)) in a method of enhancing or inducing pluripotency in a cell such as a somatic cell. We describe a method of reprogramming a cell, the method comprising modulating the expression and/or activity of Tbx3 in the cell. The cell may become a pluripotent cell such as a stem cell. We further describe a method of causing a cell such as a somatic cell to display one or more characteristics of a pluripotent cell, the method comprising modulating the expression and/or activity of Tbx3 in the cell. The method may further comprise modulating the expression and/or activity of one or more, a combination of or all of Oct4, Sox2 and Klf4 in the cell.

Abstract: The present invention relates to methods of controlling tumorigenesis, including preventing, inhibiting, arresting or reversing tumorigenesis. The present invention also provides methods of treatment, prevention and diagnosis of neoblastoma, including cancer, such as metastatic cancer. In one method one or more cells having a predisposition to turn tumorigenic are identifyied. In the one or more cells an altered amount, an altered subcellular localisation or an altered activity of a Rab binding protein is detected. In a method of diagnosing the risk of developing a neoplasmt at least one of the expression level, the activity level and the subcellular localisation of a Rab binding protein is determined. In an in-vitro method of identifying a compound capable of forming a complex with a Rab binding protein the components that form the respective complex are contacted with each other.

Abstract: Targeting metabolic enzymes in human cancer Abstract Lung cancer is a devastating disease and a major therapeutic burden with poor prognosis. The functional heterogeneity of lung cancer (different tumor formation ability in bulk of tumor) is highly related with clinical chemoresistance and relapse. Here we find that, glycine dehydrogenase (GLDC), one of the metabolic enzyme involved in glycine metabolism, is overexpressed in various subtypes of human lung cancer and possibly several other types of cancers. GLDC was found to be highly expressed in tumor-initiating subpopulation of human lung cancer cells compared with non-tumorigenic subpopulation. By array studies we showed that normal lung cells express low levels of GLDC compared to xenograft and primary tumor. Functional studies showed that RNAi inhibition of GLDC inhibits significantly the clonal growth of tumor-initiating cells in vitro and tumor formation in immunodeficient mice.

Abstract: We provide for the use of Tbx3 (GenBank Accession Number: NM_005996.3 (SEQ ID NO. 1), NP_005987.3 (SEQ ID NO. 2), NM_016569.3 (SEQ ID NO. 3), NP_057653.3 (SEQ ID NO. 4)) in a method of enhancing or inducing pluripotency in a cell such as a somatic cell. We describe a method of reprogramming a cell, the method comprising modulating the expression and/or activity of Tbx3 in the cell. The cell may become a pluripotent cell such as a stem cell. We further describe a method of causing a cell such as a somatic cell to display one or more characteristics of a pluripotent cell, the method comprising modulating the expression and/or activity of Tbx3 in the cell. The method may further comprise modulating the expression and/or activity of one or more, a combination of or all of Oct4, Sox2 and Klf4 in the cell.

Abstract: Here we demonstrate that miR-125b, a brain-enriched microRNA, is a negative regulator of p53 in animals. miR-125b-mediated downregulation of p53 is dependent on the binding of miR-125b to a microRNA response element in the 39 untranslated region of p53 mRNA. Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in cells. This phenotype can be rescued significantly by either an ablation of endogenous p53 function or ectopic expression of miR-125b in zebrafish. Ectopic expression of miR-125b suppresses the increase of p53 and stress-induced apoptosis. Together, our study demonstrates that miR-125b is an important negative regulator of p53 and p53-induced apoptosis during development and during the stress response.

Abstract: We disclose a method of promoting cartilage, bone or ligament repair or inducing repair or regeneration of chondral tissue, the method comprising enhancing the expression or activity of ZNF145 or a fragment, homologue, variant or derivative thereof in an chondrogenic progenitor cell, for example a mesenchymal stem cell. We also provide for a chondrogenic progenitor cell, for example a mesenchymal stem cell (MSC) engineered to increase expression or activity of ZNF145 or a fragment, homologue, variant or derivative thereof.