Manipulation of non-terminally differentiated cells using the notch pathway

A method for the expansion of a precursor cell comprising contacting the cell with an amount of a soluble agonist of Notch function effective to inhibit differentiation of the cell, and exposing the cell to cell growth conditions such that the cell proliferates.

A method for the expansion of a precursor cell comprising recombinantly expressing within the cell an amount of a Deltex protein or fragment thereof which binds to a Notch protein in the precursor cell effective to inhibit differentiation of the cells;

• and exposing the cell to cell growth conditions such that the cell proliferates.

A method for the expansion of a hematopoietic precursor cell comprising recombinantly expressing within the cell an amount of a Notch protein consisting essentially of the intracellular domain of a Notch protein in the precursor cell effective to inhibit differentiation;

• and exposing the cell to cell growth conditions such that the cell proliferates.

A method for the expansion of an epithelial precursor cell comprising recombinantly expressing within the cell an amount of a Notch protein consisting essentially of the intracellular domain of a Notch protein in the precursor cell effective to inhibit differentiation;

• and exposing the cell to cell growth conditions such that the cell proliferates.

A method for the expansion of a liver precursor cell comprising recombinantly expressing within the cell an amount of a Notch protein consisting essentially of the intracellular domain of a Notch protein in the precursor cell effective to inhibit differentiation;

• and exposing the cell to cell growth conditions such that the cell proliferates.

A method for the expansion of a human precursor cell comprising contacting the precursor cell with a second cell wherein the second cell recombinantly expresses on its surface a molecule consisting of at least the extracellular domain of a Notch ligand;

• and exposing the precursor cell to cell growth conditions such that the precursor cell proliferates.

A method for the expansion of an hematopoietic precursor cell comprising contacting the precursor cell with a second cell wherein the second cell recombinantly expresses on its surface a molecule consisting of at least the extracellular domain of a Notch ligand;

• and exposing the precursor cell to cell growth conditions such that the precursor cell proliferates.

A method for the expansion of a human precursor cell comprising contacting the precursor cell with an amount of a second cell expressing a Notch ligand effective to inhibit differentiation of the cell;

• and exposing the precursor cell to cell growth conditions such that the precursor cell proliferates.

A method for therapy comprising contacting a precursor cell with an effective amount of an agonist of Notch function effective to inhibit differentiation of the cell;

• exposing the cell to cell growth conditions to form an expanded precursor cell population;
• and administering a therapeutically effective amount of the expanded precursor cell population or progeny cells produced therefrom to a patient.

A method for the inhibition of a function of a signaling pathway that regulates cell growth or differentiation comprising contacting a cell with an amount of an agonist of Notch function, effective to inhibit a function of a signaling pathway in the cell that regulates cell growth or differentiation.

A method for promoting mammalian neuronal cell growth comprising contacting a mammalian neuron with an antagonist of Notch function and exposing the neuron to neuronal cell growth conditions.