Methods of using ZSCAN4 for rejuvenating human cells
The present disclosure relates to methods for increasing telomere length in one or more human adult cells and/or increasing genome stability of one or more human adult cells, for example by contacting one or more human adult cells with an agent that increases expression of Zscan4 in the one or more human adult cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a telomere abnormality, of rejuvenating one or more human adult cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human adult 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 is also provided.
1. A method of increasing telomere length in one or more human bone marrow cells or blood cells isolated from a human subject suffering from a telomere disorder with bone marrow failure, comprising introducing in vitro into the one or more human bone marrow cells or blood cells an isolated nucleic acid molecule encoding human Zscan4 wherein introduction of the isolated nucleic acid molecule encoding human Zscan4 induces telomere lengthening in the one or more human bone marrow cells or blood cells as compared to human bone marrow cells or blood cells that are not contacted with the isolated nucleic acid, and wherein the isolated nucleic acid molecule is comprised in a synthetic mRNA or a Sendai virus vector.
2. The method of claim 1 , wherein the introduction of the isolated nucleic acid molecule encoding human Zscan4 transiently increases Zscan4 activity.
3. The method of claim 1 , wherein the introduction of the isolated nucleic acid molecule encoding human Zscan4 increases Zscan4 activity for about 1 hour to about 23 hours, or for about 1 day to about 10 days.
4. The method of claim 1 , wherein the human bone marrow cells or blood cells comprise one or more of hematopoietic stem cells, mesenchymal stem cells, CD34 + cells, hematopoietic progenitor cells, endothelial progenitor cells, or any combinations thereof.
5. The method of claim 1 , wherein the isolated nucleic acid molecule is comprised in a synthetic mRNA.
6. The method of claim 1 , wherein the isolated nucleic acid molecule is comprised in a Sendai virus vector.
7. A method of engrafting bone marrow cells or blood cells in a human subject suffering from Fanconi anemia or dyskeratosis congenita, comprising:
i) introducing in vitro into human bone marrow cells or blood cells an isolated nucleic acid molecule encoding human Zscan4, wherein the human bone marrow cells or blood cells are isolated from the human subject, introduction of the isolated nucleic acid molecule encoding human Zscan4 induces telomere lengthening in the human bone marrow cells or blood cells, and the isolated nucleic acid molecule is comprised in a synthetic mRNA or a Sendai virus vector; and
ii) engrafting the human bone marrow cells or blood cells from i) into the human subject suffering from Fanconi anemia or dyskeratosis congenita.
8. The method of claim 7 , wherein the human bone marrow cells or blood cells comprise one or more of hematopoietic stem cells, mesenchymal stem cells, CD34 + cells, hematopoietic progenitor cells, endothelial progenitor cells, or any combinations thereof.
9. The method of claim 7 , wherein the isolated nucleic acid molecule is comprised in a synthetic mRNA.
10. The method of claim 7 , wherein the isolated nucleic acid molecule is comprised in a Sendai virus vector.