Abstract: Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins.

Abstract: Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins.

Abstract: Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins. Further provided are methods of prolonging and/or enhancing stem cell plmipotency using the disclosed Zscan4-ERT2 nucleic acid molecules and fusion proteins.

Abstract: Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins.

Abstract: ZSCAN4, a gene expressed in ES cells and 2-cell stage embryos, has been previously shown to regulate telomere elongation and genome stability in mouse ES cells. It is disclosed herein that in the adult human pancreas, a small number of ZSCAN4-positive cells are present among cells located in the islets of Langerhans, acini, and ducts. These data disclosed herein indicates that expression of ZSCAN4 is a marker for rare stem/progenitor cells in adult human pancreas. Thus, provided herein is a method of isolating pancreatic stem cells or progenitor cell from a sample by detecting expression of ZSCAN4. Also provided is a method of treating diabetes by isolating ZSCAN4+ pancreatic stem cells or progenitor cells, expanding the cells in vitro and transplanted the expanded cells into the subject. The expanded ZSCAN4+ cells can optionally be differentiated into pancreatic ? cells before transplanting the cells into the subject.

Abstract: Disclosed herein is the finding that Zscan4 is an early embryonic factor that facilitates cellular reprogramming. In particular, Zscan4 can replace the oncogenic reprogramming factor c-Myc to produce induced pluripotent stem cells when co-expressed with Klf4, Oct4 and Sox2. In addition, several Zscan4-dependent genes were identified that promote iPSC formation when co-expressed with known reprogramming factors. Thus, the present disclosure provides an ex vivo method of producing an iPS cell by reprogramming of a somatic cell. The method includes contacting the somatic cell with a Zscan4, or a Zscan4-dependent gene, and at least one reprogramming factor. Also provided are iPS cells produced by the disclosed method and non-human animals generated from such iPS cells.

Abstract: 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.