A novel Cbx1, PurB, and Sp3 complex mediates long-term silencing of tissue- and lineage-specific genes

Neonatal and adult cardiac fibroblasts exhibit inherent differences in cardiac regenerative capacity

“…Many researchers, including ourselves, have sought to improve efficacy through the identification and application of novel mechanistic insights. Such studies have identified potentially important roles for epigenetics and the innate immune system ( 5 , 6 , 14 , 15 , 16 , 17 ). We, and others, identified that during fibroblast to cardiomyocyte reprogramming there is a significant loss of the epigenetic motif H3K27me3 ( 5 , 14 ).…”

“…Irrespective of whether miRNAs or transcription factors are employed, functional improvements in the infarcted heart are relatively modest ( 3 , 12 , 13 ). The field has sought to improve efficacy by elucidating and then applying mechanistic insights ( 5 , 6 , 14 , 15 , 16 , 17 ). These mechanistic studies have identified important roles for various epigenetic events and innate immunity ( 5 , 6 , 14 , 15 , 16 , 17 ).…”

“…The field has sought to improve efficacy by elucidating and then applying mechanistic insights ( 5 , 6 , 14 , 15 , 16 , 17 ). These mechanistic studies have identified important roles for various epigenetic events and innate immunity ( 5 , 6 , 14 , 15 , 16 , 17 ). Mechanistic studies have solely utilized cardiac fibroblasts derived from neonatal mice as these cells are significantly easier to reprogram when compared to adult cardiac fibroblasts ( 5 , 6 , 14 , 15 , 16 , 17 ).…”

“…These mechanistic studies have identified important roles for various epigenetic events and innate immunity ( 5 , 6 , 14 , 15 , 16 , 17 ). Mechanistic studies have solely utilized cardiac fibroblasts derived from neonatal mice as these cells are significantly easier to reprogram when compared to adult cardiac fibroblasts ( 5 , 6 , 14 , 15 , 16 , 17 ). Birth appears to induce fibroblasts to undergo significant phenotypic changes ( 18 , 19 , 20 ).…”

RNA Therapeutics for the Cardiovascular System

“…It has been reported that a combination of miR-1, miR-133, miR-208, and miR-499 (miR combo) 71 is effective in reprogramming fibroblasts into cardiomyocytes both in vitro and in vivo. 7,[71][72][73][74][75][76] This was associated with modest, but significant, improvements in cardiac function in mouse models of cardiac injury. 7,8 Compared with the alternative transcription factor approaches, which are species specific, 77 miR combo effectively reprograms mouse, sheep, dog, pig, and human cardiac fibroblasts into cardiac muscle cells.…”