Ten-Eleven Translocation Ablation Impairs Cardiac Differentiation of Mouse Embryonic Stem Cells. Academic Article uri icon

abstract

  • Ten-eleven Translocation (TET) dioxygenases mediated DNA methylation oxidation plays an important role in regulating the embryonic stem cells (ESCs) differentiation. Herein, we utilized a CRISPR/Cas9 based genome editing method to generate single, double, and triple Tet-deficient mouse ESCs (mESCs) and differentiated these cells toward cardiac progenitors. By using emerald green fluorescent protein (GFP; emGFP) expression under the control of Nkx2.5 promoter as marker for cardiac progenitor cells, we discovered that Tet1 and Tet2 depletion significantly impaired mESC-to-cardiac progenitor differentiation. Single-cell RNA-seq analysis further revealed that Tet deletion resulted in the accumulation of mesoderm progenitors to hamper cardiac differentiation. Re-expression of the Tet1 catalytic domain (Tet1CD) rescued the differentiation defect in Tet-triple knockout mESCs. Dead Cas9 (dCas9)-Tet1CD mediated loci-specific epigenome editing at the Hand1 loci validated the direct involvement of Tet-mediated epigenetic modifications in transcriptional regulation during cardiac differentiation. Our study establishes that Tet-mediated epigenetic remodeling is essential for maintaining proper transcriptional outputs to safeguard mESC-to-cardiac progenitor differentiation.

published proceedings

  • Stem Cells

altmetric score

  • 0.5

author list (cited authors)

  • Fang, S., Cui, D., Hong, T., Guo, L., Lee, Y., Lee, M., ... Huang, Y.

citation count

  • 2

complete list of authors

  • Fang, Shaohai||Cui, Dan||Hong, Tingting||Guo, Lei||Lee, Yi-Tsang||Lee, Minjung||Isgandarova, Sevinj||Martinez-Moczygemba, Margarita||Zhou, Yubin||Li, Jia||Huang, Yun

publication date

  • January 2022