Methods are provided for producing differentiated cells from stem cells, including producing hepatocytes. Compositions thereof are also provided, as are methods of treating a liver disorder.

Described herein is an in vitro genetic rescue assay for identifying a functionally defective DDX41 variant which includes identifying a DEAD-Box Helicase 41 (DDX41) variant of uncertain significance (VUS), infecting a first Ddx41.sup.+/? cell with a retrovirus expressing the DDX41-VUS, infecting a second Ddx41.sup.+/? cell with a retrovirus expressing a wild type control DDX41, growing the first and second infected cells in culture for a period of time and quantitating mRNA expression of a DDX41-regulated transcript in both the first and second infected cells after the period of time, calculating a differential expression of the DDX41-regulated transcript for the first infected cell compared the second infected cell, and identifying the DDX41-VUS as the functionally defective DDX41 variant wherein a change in the differential expression is 1.5-fold or greater. The identified functionally defective DDX41 variants can be used in methods of monitoring a patient for the development/progression of myeloid malignancy.

Provided is a method of differentiating a pluripotent stem cell of mammalian origin into a desired cell type by predicting the direction of cell differentiation to be caused by induction of expression of a transcription factor. A human gene expression correlation matrix using human cells has been newly created, and further, it has been confirmed that human pluripotent stem cells can be differentiated into a desired cell type by introducing, into the human pluripotent stem cells, a transcription factor cocktail selected from the matrix.

The technology described herein is directed to methods of cryopreservation, e.g., cryopreservation in a microfluidics format and methods of utilizing cells preserved by such methods.

Provided is a method of differentiating a pluripotent stem cell of mammalian origin into a desired cell type by predicting the direction of cell differentiation to be caused by induction of expression of a transcription factor. A human gene expression correlation matrix using human cells has been newly created, and further, it has been confirmed that human pluripotent stem cells can be differentiated into a desired cell type by introducing, into the human pluripotent stem cells, a transcription factor cocktail selected from the matrix.

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Provided is a method for reprogramming human mature hepatocytes in vitro into liver progenitor cells capable of self-renewal. Disclosed is a method for preparing human liver progenitor cells, comprising culturing human mature hepatocytes in a medium containing serum, A-83-01, and CHIR99021.

Disclosed are methods of inducing formation of a liver organoid from precursor cells, such as iPSC cells. The disclosed liver organoids may be used for screening for a serious adverse event (SAE), such as liver failure and/or drug induced liver injury (DILL), and/or drug toxicity. The disclosed liver organoids may also be used to treat an individual having liver damage, or for identifying a preferred therapeutic agent.

The present invention relates to a method for delivering exogenous mitochondria into cells and, more specifically, to a method for efficiently delivering, into the cytoplasm of target cells to be injected, mitochondria isolated from donor cells.

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.