Emt-inducing transcription factors cooperate with sox9

A method of converting a cell to a less differentiated state, the method comprising:

• (a) providing a cell;
• and (b) increasing the amount or activity of at least one EMT-cooperating TF in the differentiated cell, thereby converting the cell to a less differentiated state.

A method of generating stem cells, the method comprising:

• (a) providing a population of cells that express an EMT-TF;
• and (b) contacting the cells with an agent that increases the amount or activity of at least one EMT-cooperating TF.

A method of generating stem cells, the method comprising:

• (a) providing a population of cells that express an EMT-cooperating TF;
• and (b) contacting the cells with an agent that increases the amount or activity of at least one EMT-TF.

An isolated composition or kit comprising:

• (a) an EMT-inducing agent;
• and (b) an EMT-cooperating agent.

An isolated epithelial cell comprising an exogenously introduced EMT-inducing agent and an exogenously introduced EMT-cooperating agent.

An isolated epithelial cell comprising a first exogenous nucleic acid that encodes a first polypeptide comprising an EMT-TF and a second exogenous nucleic acid that encodes a second polypeptide comprising an EMT-cooperating TF.

A method of inhibiting tumor-initiating or metastatic ability of a tumor cell the method comprising:

• contacting the tumor cell with (a) an EMT inhibitor;
• and (b) an inhibitor of an EMT-cooperating TF.

A method of treating a subject in need of treatment of a tumor, the method comprising:

• administering to the subject (a) an inhibitor of an EMT-TF;
• and (b) an inhibitor of an EMT-cooperating TF.

A method of classifying a cell, sample, or tumor, the method comprising:

• (a) assessing expression of at least two genes in the cell, sample, or tumor, wherein the first gene encodes or is regulated by an EMT-TF and the second gene encodes or is regulated by an EMT-cooperating TF, wherein increased expression of the first and second genes is correlated with a phenotypic characteristic, thereby classifying the cell, sample, or tumor with respect to the phenotypic characteristic.

A method of identifying a stem cell comprising steps of:

• (a) providing a sample comprising at least one cell;
• (b) assessing expression of a first gene that encodes an EMT-TF and a second gene that encodes or is regulated by an EMT-cooperating TF in at least one cell of the sample;
• and (c) identifying a cell that has increased expression of the first and second genes, thereby identifying a stem cell.

A method of culturing an epithelial cell, the method comprising:

• (a) providing an epithelial cell;
• (b) culturing the epithelial cell in culture medium comprising a ROCK inhibitor.

A method of culturing a stem cell, the method comprising:

• (a) providing a stem cell;
• and (b) culturing the stem cell in culture medium comprising a ROCK inhibitor.

A composition or kit comprising a ROCK inhibitor and an isolated EMT-inducing agent.

A composition comprising a ROCK inhibitor and about 5% Matrigel or an equivalent thereof.

A method of obtaining an organoid from a stem cell, the method comprising culturing a stem cell in a composition comprising about 5% Matrigel or an equivalent thereof.

A composition comprising at least one organoid in a composition comprising about 5% Matrigel or an equivalent thereof.

A method of treating a subject comprising:

• (a) obtaining stem cells or differentiated epithelial cells according to the method of any of claims, and (b) introducing at least some of the cells into a subject in need thereof.

The method of any of the foregoing claims that pertain at least in part to a subject, wherein the subject is human.

The method of any of the foregoing claims that pertain at least in part to an EMT-TF or EMT-cooperating protein, wherein the EMT-TF or EMT-cooperating protein is human.