A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.

Methods and compositions are provided for the treatment of a mitochondrial disease in an individual with the mitochondrial disease. Aspects of the methods include administering an inhibitor of a Pumilio-like protein and/or an inhibitor of a serine/arginine-rich family of pre-mRNA splicing factor (SR) protein to a subject. Also provided are methods, compositions, systems and kits for transdifferentiating target cells to neurons, which find use in producing neurons for the development of new therapies, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example, for use in treating human disorders of the CNS.

The present invention provides methods of transdifferentiation of somatic cells, for example, directly converting a somatic cell of a first cell type, e.g., a fibroblast into a somatic cell of a second cell type, are described herein. In particular, the present invention generally relates to methods for converting a somatic cell, e.g., a fibroblast into a motor neuron, e.g., an induced motor neuron (iMN) with characteristics of a typical motor neuron. The present invention also relates to an isolated population comprising induced motor neurons (iMNs), compositions and their use in the treatment of motor neuron diseases such as ALS and SMA. In particular, the present invention relates to direct conversion of a somatic cell to an induced motor neuron (iMN) having motor neuron characteristics by increasing the protein expression of at least three motor-neuron inducing (MN-inducing) factors selected from Lhx3, Ascl1, Brn2, Myt1l, Isl1, Hb9, Ngn2 or NeuroD1 in a somatic cell, e.g., a fibroblast to convert the fibroblast to an induced motor neuron (iMN) which exhibits at least two characteristics of an endogenous motor neuron.

A method of generating protein-induced pluripotent stem cells by delivering bacterially expressed reprogramming proteins into nuclei of starting somatic cells using the QQ-protein transduction technique, repeating several cell reprogramming cycles for creating reprogrammed protein-induced pluripotent stem cells, moving the reprogrammed cells into a feeder-free medium for expansion, and expanding and passaging the reprogrammed cells in a whole dish for generating homogeneous piPS cells. Also provided are the piPCS cells formed using this method and uses thereof.

The present invention relates to a method for producing cholinergic neurons comprising obtaining neural progenitor cells from stem cells so as to continuously produce cholinergic neural cells with high purity and the same traits, followed by differentiating the neural progenitor cells into the cholinergic neurons, and cholinergic neurons produced therefrom. Since the method of preparing the cholinergic neurons provided in the present invention enables not only production of the cholinergic neurons with high purity, but also rapid production of the cholinergic neurons with the same traits, it can be widely used for effectively treating degenerative cranial nerve diseases such as Alzheimer's disease.

A method of producing induced pluripotent stem cells including a step for introducing an initialization factor into somatic cells of a mammal, and culturing in a neural stem cell culture medium to obtain induced neural stem cell-like cells, and a step for cultivating said induced neural stem cell-like cells in a growth medium to obtain induced pluripotent stem cells, wherein the initialization factor contains an OCT family, a SOX family, a KLF family, a MYC family, a LIN28 family and a P53 function inhibitor.

The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.

The present disclosure provides compositions and methods of using gene therapy to create induced pluripotent stem cells (iPSCs) without inducing cancer or tumorigenesis. The methods disclosed herein employ plasmids and vectors that contain transcription factors and an anti-oncogene such as PCBP1 which inhibits the expression of cancer biomarkers and concomitant oncogenesis.

It is a main object of the present invention to provide a process for producing an insulin-producing cell from a somatic cell without performing artificial gene transfer, an insulin-producing cell obtained from the process, or a composition comprising a combination of chemical substances that can be used for the process. The present invention can include, for example: a process for producing an insulin-producing cell from a somatic cell by direct differentiation induction, comprising a step of culturing a somatic cell in the presence of an RSK inhibitor; an insulin-producing cell obtained from the process; and a composition for producing an insulin-producing cell from a somatic cell by directly inducing differentiation, comprising an RSK inhibitor. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.

The present invention pertains to a method for producing induced pluripotent stem cells, and more specifically, to a method for producing induced pluripotent stem cells using RNA nanoparticles for cell transformation, wherein: cell transformation can be effectively performed without genetic modification by producing induced pluripotent stem cells using self-assembled RNA nanoparticles including at least one RNA selected from the group consisting of messenger RNA for expressing transcription factors which induce somatic cells and adult stem cells to be dedifferentiated into induced pluripotent stem cells, micro RNA facilitating the dedifferentiation process, and small interfering RNA; the production efficiency of iPSCs can be maximized by adjusting structural properties and activity; and low gene loading efficiency can be overcome by applying an infinite replication process to incorporate high concentrations of RNA in RNA nanoparticles.