Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

In some aspects and embodiments, the invention provides methods for making hematopoietic stem cells, including for HSCT. The method comprises providing a cell population comprising hemogenic endothelial (HE) or endothelial cells, and increasing activity or expression of DNA (cytosine-5-)-methyltransferase 3 beta (Dnmt3b) and/or GTPase IMAP Family Member 6 (Gimap6) in the HE and/or endothelial cells under conditions sufficient for stimulating formation of HSCs.

The present invention provides a method for artificially producing a vascular endothelial stem cell from a non-vascular endothelial stem cell. The method for producing a vascular endothelial stem cell of the present invention comprises the step of bringing a vascular endothelial cell possessing no stem cell properties into contact with a factor secreted by an organ of a neonatal or juvenile mammal. The step may be a step of (1) transplanting the vascular endothelial cell possessing no stem cell properties into the organ of the neonatal or juvenile mammal, wherein the mammal is a non-human mammal, or (2) culturing the vascular endothelial cell possessing no stem cell properties in a culture system containing the factor secreted by the organ of the neonatal or juvenile mammal.

In some aspects and embodiments, the invention provides methods for making hematopoietic stem cells, including for HSCT. The method comprises providing a cell population comprising hemogenic endothelial (HE) or endothelial cells, and increasing activity or expression of DNA (cytosine-5-)-methyltransferase 3 beta (Dnmt3b) and/or GTPase IMAP Family Member 6 (Gimap6) in the HE and/or endothelial cells under conditions sufficient for stimulating formation of HSCs.

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 invention generally relates to novel preparations of mesenchymal stromal cells (MSCs) derived from hemangioblasts, methods for obtaining such MSCs, and methods of treating a pathology using such MSCs. The methods of the present invention produce substantial numbers of MSCs having a potency-retaining youthful phenotype, which are useful in the treatment of pathologies.

A method for inducing conversion from non-hepatic stem cells or non-hepatic progenitor cells into hepatic stem cells or hepatic progenitor cells, which comprises introducing any of the following combinations into the non-hepatic stem cells or non-hepatic progenitor cells: (a) a combination of HNF1, HNF6 and FOXA; (b) a combination of HNF1 gene, HNF6 gene and FOXA gene; (c) a combination of HNF1, MYC and FOXA; or (d) a combination of HNF1 gene, MYC gene and FOXA gene.

The nuclear reprogramming of somatic cells with mRNA encoding reprogramming factors is shown to be greatly accelerated by activation of innate immune responses in the somatic cell. Methods of activating innate immunity include activation of PKR, of toll-like receptors, e.g. TLR3, etc. In some embodiments the mRNA provides the activator of innate immunity.

The present invention provides for methods, compositions, and kits for producing an induced pluripotent stem cell from a non-pluripotent mammalian cell using a 3′-phosphoinositide-dependent kinase-1 (PDK1) activator or a compound that promotes glycolytic metabolism as well as other small molecules.

The disclosure relates to compositions comprising hematopoietic cells and methods of using the same. The disclosure also relates to methods of reprogramming endothelial cells into hematopoietic cells by exposing the endothelial cells to at least one hematopoietic effector.