A method for producing pancreatic endocrine cells, including introducing (A), (B), (C), or (D) into somatic cells: (A) mutated GLIS1 gene having 85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, Pdx1 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof; (B) mutated GLIS1 gene having 85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, and Pdx1 gene or gene product(s) thereof (C) GLIS1 gene or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, Pdx1 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof and (D) mutated GLIS1 gene having 85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mesp1, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mesp1, Mesp2, Gata4, Gata6, Baf60c, SRF, Isl1, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

Described herein are methods of generating induced muscle progenitor cells (iMPCs) and uses thereof. Embodiments further provide for methods of promoting muscle regeneration and/or repair and methods of treating a muscle disease or disorder.

Expression of exogenous SNAI2, EYA1 and SIX1 genes in a cell, tissue or organ not normally having nephron progenitor activity, induces or re-programs that cell to have or subsequently develop nephron progenitor activity. Nephron progenitors induced 5 by expression of SNAI2, EYA1 and SIX1 may be used for the production of nephron cells and tissues that are useful in treatment of kidney disorders, kidney regeneration, kidney transplantation, bioprinting and nephrotoxocity testing.

The present invention provides methods for delivering a transient and/or reversible complex into a cell including passing a cell suspension through a constriction, wherein said constriction deforms the cell, thereby causing a perturbation of the cell such that the complex enters the cell.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

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.

The present invention relates to an adult stem cell line introduced with an HGF gene and a neurogenic transcription factor gene of a bHLH family, a preparation method of the adult stem cell line, a composition for the prevention or treatment of neurological diseases comprising the adult stem cell line, and a method for treating neurological diseases comprising the step of administering the composition to a subject having neurological diseases or suspected of having neurological diseases. The adult stem cells according to the present invention, which are introduced with an HGF gene and a neurogenic transcription factor gene of a bHLH family, can be used to overcome chronic impairment caused by cell death following stroke. Thus, the adult stem cells can be developed as a novel therapeutic agent or widely used in clinical trial and research for cell replacement therapy and gene therapy that are applicable to neurological diseases including Parkinson's disease, Alzheimer disease, and spinal cord injury as well as stroke.