Nucleic acid sequences associated with cell states
The present invention is directed to nucleic acid sequences whose expression is associated with different cell states, including nucleic acid sequences whose expression is induced at least 100-fold, or alternatively upregulated, in cells exhibiting asymmetric self-renewal relative to other cells. The invention is also directed to nucleic acid sequences whose expression is induced at least 100-fold, or alternatively upregulated, in cells exhibiting symmetric self-renewal relative to other cells.
1. A method for identifying a cell exhibiting asymmetric self-renewal comprising measuring the expression level of at least 20 nucleic acid sequences, or measuring the expression level of a mammalian homologue of each of the 20 nucleic acid sequences, wherein the 20 nucleic acid sequences are identified by the following SEQ ID NOs: SEQ ID NO: 231, SEQ ID NO: 298, SEQ ID NO:303, SEQ ID NO: 338, SEQ ID NO: 275, SEQ ID NO: 261, SEQ ID NO: 339, SEQ ID NO: 262, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 288, SEQ ID NO: 219, SEQ ID NO: 243, SEQ ID NO: 216, SEQ ID NO: 221, SEQ ID NO: 297, SEQ ID NO: 250, SEQ ID NO: 237, SEQ ID NO: 232, SEQ ID NO: 218; and
wherein an increase in expression level relative to isogenic cells not undergoing asymmetric replication of said nucleic acids is indicative of a cell exhibiting asymmetric self-renewal.
2. The method of claim 1 , further comprising measuring the expression level of at least 18 additional nucleic acid sequences, or measuring the expression level of a mammalian homologue of each of the 18 nucleic acid sequences, wherein the 18 nucleic acid sequences are identified by the following SEQ ID NOs:
SEQ ID NO: 242, SEQ ID NO: 247, SEQ ID NO: 387, SEQ ID NO: 224, SEQ ID NO: 355, SEQ ID NO: 402, SEQ ID NO: 266, SEQ ID NO: 327, SEQ ID NO: 391, SEQ ID NO: 238, SEQ ID NO: 334, SEQ ID NO: 271, SEQ ID NO: 263, SEQ ID NO: 310, SEQ ID NO: 352, SEQ ID NO: 358, SEQ ID NO: 267, SEQ ID NO: 365;
and wherein an increase in expression level relative to isogenic cells not undergoing asymmetric replication of said nucleic acids is indicative of a cell exhibiting asymmetric self-renewal.
3. The method of claim 1 , wherein the mammalian homologue is a human homologue.
4. The method of claim 1 , wherein an at least 50 fold increase in expression level relative to isogenic cells not undergoing asymmetric replication of said nucleic acids is indicative of a cell exhibiting asymmetric self-renewal.
5. The method of claim 1 , wherein an at least 100 fold increase in expression level relative to isogenic cells not undergoing asymmetric replication of said nucleic acids is indicative of a cell exhibiting asymmetric self-renewal.
6. The method of claim 1 , wherein the cell is in a population of cells.
7. The method of claim 1 , wherein the nucleic acid sequences are amplified.
8. The method of claim 1 , wherein said expression level is measured using a method selected from the group consisting of: Northern-blot hybridization, ribonuclease protection assay, reverse transcriptase polymerase chain reaction (RT-PCR), competitive polymerase chain reaction, ion-pair high-performance liquid chromatography, real-time RT-PCR, and nucleic acid array analysis.
9. The method of claim 1 , wherein the expression level is measured using a fluorescent signal.
10. The method of claim 1 , wherein the expression level is determined by measuring the expression level of a protein encoded by the nucleic acid sequence or corresponding human homolog.
11. The method of claim 1 , wherein the expression level is measured using a fluorescent signal.
12. The method of claim 1 , wherein the cell is a somatic stem cell.
13. The method of claim 1 , further comprising measuring the expression level of at least 6 additional nucleic acid sequences, or measuring the expression level of a mammalian homologue of each of the 6 nucleic acid sequences, wherein the 18 nucleic acid sequences are identified by the following SEQ ID NOs: SEQ ID NO: 6, SEQ ID NO: 16, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 70, and SEQ ID NO: 83, and wherein an increase in expression level relative to isogenic cells not undergoing asymmetric replication of said nucleic acids is indicative of a cell exhibiting asymmetric self-renewal.