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. A method of treating bone marrow failure associated with Fanconi anemia, dyskeratosis congenita or Hoyeraal-Hreidarsson syndrome, comprising:
i. contacting one or more human bone marrow or blood cells with an isolated nucleic acid molecule encoding Zscan4 or a Zscan4 protein, and wherein the isolated nucleic acid molecule encoding the Zscan4 or the Zscan4 protein induces extension of telomeres in the one or more human bone marrow or blood cells; and
ii. engrafting the contacted one or more human bone marrow or blood cells into the subject to treat the bone marrow failure associated with the Fanconi anemia, dyskeratosis congenita or Hoyeraal-Hreidarsson syndrome, wherein the bone marrow failure is caused by telomere shortening, and wherein the associated bone marrow failure is ameliorated.
2. The method of claim 1 , wherein the one or more human bone marrow or blood cells are isolated from the subject suffering from the Fanconi anemia, dyskeratosis congenita or Hoyeraal-Hreidarsson syndrome.
3. 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.
4. The method of claim 3 , wherein the isolated nucleic acid molecule is a synthetic mRNA.
5. The method of claim 3 , wherein the isolated nucleic acid molecule is comprised in a vector.
6. The method of claim 5 , wherein the vector is a Sendai virus vector.
7. The method of claim 3 , wherein the Zscan4 is a Zscan4-ERT2 fusion protein or a Zscan4-ΔC protein.
8. The method of claim 3 , wherein the Zscan4 is mouse Zscan4, human ZSCAN4, or a homolog thereof.
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. The method of claim 9 , wherein the Zscan4 protein is a mouse Zscan4 protein or a human ZSCAN4 protein.
12. The method of claim 1 , wherein the blood cells are peripheral blood cells.