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.

The invention provides a method of producing a connective tissue graft suitable for correcting a connective tissue defect, comprising determining the size and shape of a tissue defect, obtaining a fat tissue from a patient modelled to fit the size and shape of the tissue defect, contacting the fat tissue with one or more connective tissue specific growth or differentiation factors; and kits for such a method.

The invention provides in certain embodiments, a method of generating a re-programmed differentiated epithelial cell comprising (a) contacting a non-stem somatic cell obtained from a subject with an effective amount of a de-differentiation agent to form a de-differentiated cell, and (b) transfecting the de-differentiated cell with an expression cassette comprising a promoter operably linked to a nucleic acid encoding a conversion agent to form a re-programmed differentiated cell. The invention also provides in certain embodiments, a method of generating a re-programmed differentiated epithelial cell comprising (a) contacting a non-stem somatic cell obtained from a subject with an effective amount of a de-differentiation agent to form a de-differentiated cell, and (b) contacting the de-differentiated cell with a conversion agent to form a re-programmed differentiated cell. The invention provides in certain embodiments, re-programmed differentiated epithelial cells, and methods of using these re-programmed differentiated epithelial cells to repair or re-generate tissue in vivo.

The present disclosure provides methods of producing a preparation of fibroadipogenic progenitors (FAPs) from a cell mixture. In certain embodiments, the present disclosure provides a method of producing a preparation of human FAPs from a skeletal muscle biopsy sample for later use.

Provided are an in vitro fibrosis model, a method of preparing the in vitro model, and use of the in vitro model, the in vitro model including a cell cluster differentiated from mesenchymal cells, wherein the cell cluster exhibits pathological characteristics of fibrosis.

Provided is reproducible means that enables the production of an active nucleus pulposus cell phenotype from desired cells such as terminally differentiated cells or pluripotent or multipotent stem cells. Provided is a differentiation inducer containing an effective amount of a gene of at least two transcription factors selected from the group consisting of Brachyury (T), SRY-box6 (SOX6), C and Forkhead Box Q1 (FOXQ1), or homologs thereof (nucleus pulposus cell master regulator transcription factor), or a product thereof.

A reagent for differentiating somatic cells into alveolar epithelial cells includes an NK2 homeobox family gene expression vector, and a Fox family gene expression vector, a method for manufacturing alveolar epithelial cells, the method including forcing a somatic cell to express an NK2 homeobox family gene and a Fox family gene and culturing the somatic cell after forced expression, an alveolar epithelial cell manufactured by the manufacturing method, and a cell medicine including the alveolar epithelial cell.

The present disclosure provides an iPSC cell derived from a somatic cell comprising a Cbx family gene and the applications thereof. Also provided are methods for generating the somatic cells that have potential to become induced pluripotent stem (iPS) cells (iPS cells) without oncogenic properties, and methods for generating iPS cells from the population of cells, which may then be used for transplantation and for cellular differentiation and interaction.

Provided herein are recombinant circular RNAs comprising at least one protein-coding nucleic acid sequence, wherein the protein-coding nucleic acid sequence encodes a reprogramming factor (e.g., a transcription factor), wherein the reprogramming factor is Oct3/4, Klf4, Sox2, Nanog, Lin28, c-Myc, or L-Myc, or a fragment or variant thereof. Also provided herein are methods of producing induced pluripotent stem cells (iPSC), the method comprising contacting a somatic cell with at least one of the recombinant circular RNAs described herein and maintaining the cell under conditions under which a reprogrammed iPSC is obtained.

A method of producing an induced pluripotent stem cell, comprising the step of introducing at least one kind of non-viral expression vector incorporating at least one gene that encodes a reprogramming factor into a somatic cell. In some embodiments, the gene that encodes a reprogramming factor is one or more kind of genes selected from the group consisting of an Oct family gene, a Klf family gene, a Sox family gene, a Myc family gene, a Lin family gene, and the Nanog gene.