Methods of using ZSCAN4 for rejuvenating human cells
The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.
1. An in vitro method of treating a disease or condition with a karyotype abnormality, comprising:
contacting one or more human bone marrow or blood cells with an isolated nucleic acid molecule encoding Zscan4 or a Zscan4 protein, wherein the one or more human bone marrow or blood cells are isolated from a subject suffering from the disease or condition with the karyotype abnormality, and wherein the isolated nucleic acid molecule encoding Zscan4 or the Zscan4 protein induces correction of the karyotype abnormality in the one or more human bone marrow or blood cells,
wherein the karyotype abnormality is selected from the group consisting of a chromosome trisomy, a XXX aneuploidy, a XXY aneuploidy, and a XYY aneuploidy, and the disease or condition with the karyotype abnormality is a bone marrow failure.
2. The method of claim 1 , wherein the karyotype abnormality is a chromosome trisomy selected from the group consisting of trisomy 21, trisomy 16, trisomy 18, and trisomy 13.
3. The method of claim 1 , wherein the karyotype abnormality is trisomy 21.
4. The method of claim 1 , wherein the one or more human bone marrow or blood cells are mesenchymal stem cells, CD34 + cells, hematopoietic stem cells, hematopoietic progenitor cells, endothelial progenitor cells, or any combinations thereof.
5. The method of claim 1 , wherein the one or more human bone marrow or blood cells are contacted with the isolated nucleic acid molecule encoding Zscan4.
6. The method of claim 1 , wherein the one or more human bone marrow or blood cells are contacted with the isolated nucleic acid molecule encoding Zscan4, and the isolated nucleic acid molecule is comprised in a vector.
7. The method of claim 6 , wherein the vector is a Sendai virus vector.
8. The method of claim 1 , wherein the blood cells are peripheral blood cells.
9. The method of claim 1 , wherein the one or more human bone marrow or blood cells are contacted with the Zscan4 protein.
10. The method of claim 9 , wherein the Zscan4 protein is fused to a cell-penetrating peptide.
11. An in vitro method of correcting a karyotype abnormality in one or more human non-embryonic cells, comprising:
contacting one or more human non-embryonic cells with an isolated nucleic acid molecule encoding Zscan4, wherein the one or more human non-embryonic cells have the karyotype abnormality, and wherein the isolated nucleic acid molecule encoding Zscan4 induces correction of the karyotype abnormality in the one or more human non-embryonic cells; and
wherein the karyotype abnormality is selected from the group consisting of a chromosome trisomy, a XXX aneuploidy, a XXY aneuploidy, and a XYY aneuploidy.
12. The method of claim 11 , wherein the karyotype abnormality is a chromosome trisomy selected from the group consisting of trisomy 21, trisomy 16, trisomy 18, and trisomy 13.
13. The method of claim 11 , wherein the karyotype abnormality is trisomy 21.
14. The method of claim 11 , wherein the one or more human non-embryonic cells are contacted with the isolated nucleic acid molecule encoding Zscan4, and the isolated nucleic acid molecule is a synthetic mRNA.
15. The method of claim 11 , wherein the one or more human non-embryonic cells are contacted with the isolated nucleic acid molecule encoding Zscan4, and the isolated nucleic acid molecule is comprised in a vector.
16. The method of claim 15 , wherein the vector is a Sendai virus vector.
17. The method of claim 11 , wherein the one or more human non-embryonic cells are adult stem cells, tissue stem cells, or progenitor cells.
18. The method of claim 17 , wherein the progenitor cells are selected from the group consisting of hematopoietic stem cells, mesenchymal stem cells, adipose stem cells, and neuronal stem cells.