Stem-cell based biomarker discovery

A method comprising:

• a) xenotransplanting genetically modified differentiated cells into an area of interest in an animal model;
• wherein the differentiated cells comprise a genetically modified Uracil PhosphoRibosylTransferase (UPRT) enzyme;
• b) treating the animal model with an RNA analog;
• c) extracting total RNA from the area of interest in the animal model;
• d) producing a fraction of the RNA extracted in (c) by:
• i) attaching a label to the RNA comprising the RNA analog;
• and
• ii) isolating the labeled RNA from the total RNA extracted from the area of interest in the animal model;
• and
• e) analyzing the RNA isolated from (d).

A method comprising:

• a) xenotransplanting genetically modified differentiated cells into an area of interest in an animal model;
• wherein the differentiated cells comprise a genetically modified Uracil PhosphoRibosylTransferase (UPRT) enzyme;
• b) treating the animal model with an uracil analog;
• c) extracting total RNA from the area of interest in the animal model;
• d) producing a fraction of the RNA extracted in (c) by:
• i) attaching a label to the RNA comprising the uracil analog;
• and
• ii) isolating the labeled RNA from the total RNA extracted from the area of interest in the animal model;
• and
• e) analyzing the RNA isolated from (d).

A method comprising:

• a) xenotransplanting genetically modified differentiated cells into an area of interest in an animal model;
• b) treating the animal model with an amino acid analog;
• c) extracting total protein from the area of interest in the animal model;
• d) producing a fraction of the protein extracted in (c) by:
• i) attaching a label to the protein comprising the amino acid analog;
• and
• ii) isolating the labeled protein from the total protein extracted from the area of interest in the animal model;
• and
• e) analyzing the protein isolated from (d).

A method comprising:

• a) xenotransplanting genetically modified differentiated cells into an area of interest in an animal model;
• wherein the differentiated cells comprise a genetically modified Methionine tRNA Synthase (MetRS) enzyme.
• b) treating the animal model with an amino acid analog;
• c) extracting total protein from the area of interest in the animal model;
• d) producing a fraction of the protein extracted in (c) by:
• i) attaching a label to the protein comprising the amino acid analog;
• and
• ii) isolating the labeled protein from the total protein extracted from the area of interest in the animal model;
• and
• e) analyzing the protein isolated from (d).

A method comprising:

• a) xenotransplanting genetically modified differentiated cells into an area of interest in an animal model;
• b) treating the animal of the model with an RNA and/or an amino acid analog;
• c) extracting total RNA and/or total protein from the area of interest in the animal model;
• d) producing a fraction of the RNA and/or the protein extracted in (c) by:
• i) attaching a label to the RNA and/or the protein comprising the RNA analog and/or the amino acid analog;
• and
• ii) isolating the labeled RNA and/or the labeled protein from the total RNA and/or the total protein extracted from the area of interest in the animal model;
• and
• e) analyzing the RNA and/or protein isolated from (d)

A method comprising:

• a) xenotransplanting human pluripotent stem cell derived microglia (iMGL) into an animal model's brain;
• wherein the iMGL comprise a genetically modified Uracil PhosphoRiboxylTransferase (UPRT) enzyme;
• b) treating the animal of the model with an uracil analog;
• c) extracting total RNA from the animal model's brain;
• d) producing a fraction of the RNA extracted in (c) by:
• i) attaching a label to the RNA comprising the uracil analog;
• and
• ii) isolating the labeled RNA from the total RNA extracted from the brain;
• e) analyzing the RNA isolated from (d).