Abstract: This invention concerns chemically defined haematopoietic induction media that support the differentiation of haemogenic endothelial cells (HECs) into haematopoietic progenitor cells (MFCs) that are capable of further differentiation into T cells. The media may (a) stimulate cKIT receptor and/or cKIT receptor mediated signalling pathways and/or (b) stimulate VEGFR and/or VEGFR mediated signalling pathways. For example, the medium may comprise SCF and VEGF. In some embodiments, the media may further (c) stimulate MPL or MPL mediated signalling pathways; (d) stimulate FLT3 or FLT3 mediated signalling pathways (e) stimulate IGF1R or IGF1R mediated signalling pathways and (f) display interleukin (IL) activity. For example, the medium may further comprise Thrombopoietin (TPO), Fits ligand (FltSL), IGF-1, IL-3, IL-6 and optionally IL-7. These media may be useful for example in the production of blood cells or use in immunotherapy.

Abstract: This invention relates to the differentiation of recombination activating gene (RAG) inactivated progenitor cells into T cells through the expression of an exogenous T Cell Receptor (TCR). A population of T cells may be produced by a method that comprises (i) differentiating a population of RAG inactivated induced pluripotent stem cells (IPSCs) into mesoderm cells, (ii) differentiating the mesoderm cells (MCs) to produce a population of haemogenic endothelial cells (HECs), (iii) differentiating the HECs into a population of haematopoietic progenitor cells (HPCs), (iv) differentiating the population of HECs into progenitor T cells; and (v) maturing the progenitor T cells to produce a population of double positive CD4+CD8+ T cells. The method may further comprise introducing a heterologous nucleic acid encoding an antigen receptor, such as a T Cell Receptor (TCR) or chimeric antigen receptor (CAR), into one of the RAG inactivated (a) IPSCs (b) MCs (c) HECs (d) HPCs or (e) the progenitor T cells.

Abstract: This invention relates to the production of a population of haemogenic progenitor cells by (i) differentiating a population of induced pluri potent stem cells (IPSCs) into mesoderm cells and; (II) differentiating the mesoderm cells to produce a population of haemogenic progenitor cells. Steps (i) and (ii) are performed without purification or isolation of cells in the population. In addition, the haemogenic progenitor cells may be produced without the use of serum or stromal co-culture. Methods of the invention may be useful for example, in the production of clinical grade blood cells, such as T cells, for use in immunotherapy.

Abstract: A screen using RNAi methods was used to test the entire set of protein kinases in Drosophila for an effect on mitosis. Most kinases previously known to be involved in the cell cycle were identified, providing validation of the approach. A mitotic function was found for a number of kinases not previously known to be involved in the cell cycle. Materials and methods are therefore provided for control of the cell cycle using modulators of expression or activity of kinases not previously known to act in mitosis, including human orthologues thereof.