The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

Disclosed are findings that: (a) induced pluripotent stem cells derived from aged donors (A-iPSC) show increased genomic instability, a defect in apoptosis, a defect in glucose metabolism, and a blunted DNA damage response are compared to those derived from young donors (Y-iPSC); and (b) inhibition of excessive glutathione-mediated H.sub.2O.sub.2 scavenging activity, found to be associated with A-iPSC and in turn inhibiting DNA damage response and apoptosis, substantially rescues these defects and reduces the oncogenic potential of A-iPSC. Supplementation of pluripotency factor ZSCAN10 (shown to be poorly activated in A-iPSC and to act upstream of glutathione involvement), e.g., by expression as an adjunct to the four Yamanaka iPSC reprogramming factors, led to substantial recovery of genomic stability, DNA damage response, and apoptosis in A-iPSC through enhancing GLUT3 and normalizing homeostasis of glutathione/H.sub.2O.sub.2; GLUT3 (a pluripotent stem cell-specific glucose transporter acting upstream of glutathione and also poorly activated in A-iPSC) has similar effects, indicating that inhibition of glutathione/H.sub.2O.sub.2 notably through delivery of ZSCAN 10 and/or GLUT3 and/or an exosome subunit will be clinically useful, resulting in A-iPSC of improved properties and reduced oncogenic potential.

The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

A culture medium is disclosed which comprises STAT3 activator, an ERK1/2 inhibitor and an Axin stabilizer, and optionally also a PKC inhibitor. Cell cultures comprising same and uses thereof are also disclosed.

Provided is a method for producing chondrocytes from pluripotent stem cells, the method comprising the steps of: (i) culturing pluripotent stem cells under adherent conditions in a medium containing an HMG-CoA reductase inhibitor and one or more substances selected from the group consisting of BMP2, TGF and GDF5, and (ii) culturing the cells obtained in step (i) under suspension conditions in a medium containing an HMG-CoA reductase inhibitor and one or more substances selected from the group consisting of BMP2, TGF and GDF5.

Also provided is a pharmaceutical product comprising chondrocytes obtained by the method.

The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

Provided herein are methods and kits for measuring a level of a 5-hydroxymethylcytosine in a nucleotide sequence from a subject, wherein the subject is a subject having a cancer or suspected of having cancer.

Provided herein are methods and kits for measuring a level of a 5-hydroxymethylcytosine in a nucleotide sequence from a subject, wherein the subject is a subject having a cancer or suspected of having cancer.

The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

The present disclosure pertains to compositions suitable for use in differentiating cardiac progenitor cells to cells that resemble cardiac Purkinje cells. Additional embodiments pertain to methods of generating such differentiated cardiac cells by exposing cardiac progenitor cells to the compositions. The present disclosure also pertains to methods of treating or preventing a cardiovascular disease in a subject by administering the compositions or differentiated cardiac cells to the subject. Further embodiments pertain to methods of generating a cardiac tissue by exposing cardiac progenitor cells to a composition of the present disclosure and associating the cardiac progenitor cells with a tissue scaffold. The present disclosure also pertains to the use of the differentiated cardiac progenitor cells to assess the efficacy of one or more compounds in the treatment or prevention of a cardiovascular disease. The present disclosure also pertains to the differentiated cardiac cells and cardiac tissues that include them.