Long noncoding RNAS and cell reprogramming and differentiation
Long noncoding RNAs (lncRNAs) are identified that enhance pluripotency reprogramming of somatic cells as well as differentiation of pluripotent cells. Induced pluripotent stem (iPS) cell generation from somatic cells leads to the upregulation and downregulation of identified lncRNAs. The modulation of these lncRNAs are capable of enhancing pluripotency of somatic cells as well as enhancing differentiation of a pluripotent cell.
1. A method of enhancing reprogramming of a somatic cell to a pluripotent cell in a human or mouse, comprising:
upregulating in the somatic cell at least one long noncoding RNA (lncRNA) selected from SEQ ID NOs. 43, 272, 304, 334, 345, 395, and homologs thereof having at least 85% homology to the at least one lncRNA, the upregulating comprising adding or activating the at least one lncRNA.
2. The method of claim 1 , wherein the adding or activating comprises contacting the somatic cell with the at least one synthetic lncRNA and/or a vector encoding the at least one lncRNA.
3. The method of claim 1 , further comprising downregulating in the somatic cell at least one lncRNA selected from SEQ ID NOs. 361, 408, 414, 415, 418, 419, and homologs thereof having at least 85% homology to the at least one lncRNA, the downregulating comprising contacting the somatic cell with antisense oligonucleotides and/or interfering RNA (RNAi) targeting the at least one lncRNA.
4. The method of claim 3 , wherein the somatic cell is human and the upregulating of the at least one lncRNA comprises upregulating lncRNAs selected from SEQ ID NOs. 334, 345, 395, and the homologs thereof having at least 85% homology to the at least one lncRNA, and the downregulating of the at least one lncRNA comprises contacting the somatic cell with antisense oligonucleotides and/or interfering RNAi targeting the at least one lncRNA selected from SEQ ID NOs. 361, 408, 414, and the homologs thereof having at least 85% homology to the at least one lncRNA.
5. The method of claim 1 , further comprising expressing Oct 4, Sox2, Klf4, and c-Myc transcription factors in the somatic cell.
6. The method of claim 1 , wherein the homologs have at least 90% homology.
7. A method of enhancing differentiation of a cell in a pluripotent state in a human or mouse, comprising:
downregulating in the cell at least one long noncoding RNA (lncRNA) selected from SEQ ID NOs. 272, 304, 334, 395, and homologs thereof having at least 85% homology to the at least one lncRNA, the downregulating comprising contacting the cell with antisense oligonucleotides and/or interfering RNA (RNAi) targeting the at least one lncRNA.
8. The method of claim 7 , further comprising upregulating at least one lncRNA selected from SEQ ID NOs. 361, 408, 414, 415, 418, 419, and homologs thereof having at least 85% homology to the at least one lncRNA, the upregulating comprising adding or activating the at least one lncRNA.