Generation of a homozygous TET2 knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential (CHIP)

Atherosclerotic cardiovascular diseases (CVD) have been linked to mutations related to clonal hematopoiesis of indeterminate potential (CHIP), with Tet methylcytosine dioxygenase 2 (TET2) being the second most often altered gene. (Jaiswal et al. 2017; Abplanalp et al. 2021) We produced a genome-edited human induced pluripotent stem cell (hiPSC) line with a homozygous knock-out (KO) of TET2, simulating loss-of-function mutations, and a control line. We evaluated the pluripotency status of these lines and their capacity to differentiate into mesoderm, ectodem and endoderm. Analysis of the cellular pathomechanisms of TET2-related, CHIP-associated CVDs is made possible by the generation of these cell lines.