#CFS TO CMS SKIN#
TAp63 controls skin homeostasis by maintaining dermal and epidermal progenitor/stem cell pool and protecting them from senescence, DNA damage and genomic instability, whereas the second study is related to the role of TAp63, expressed by the primitive endoderm, on heart development ( 13). The first discovery is related to the protective role of TAp63 on premature aging. Recent studies have demonstrated novel functions for TAp63 that could have potential implications to human pathologies. Therefore, the balance of various p53 family isoforms may determine cell fate.
![cfs to cms cfs to cms](https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs00395-021-00854-y/MediaObjects/395_2021_854_Fig1_HTML.png)
N-truncated isoforms of p63 (DNp63) and p73 (DNp73) support self-renewal of the stem cells, while full-length isoforms of p53, p63 (TAp63), and p73 (TAp73) induce differentiation ( 12). It is crucial for this activity that p53 family members are expressed as two groups of proteins with opposing activity.
![cfs to cms cfs to cms](https://img.directindustry.fr/images_di/photo-g/63036-14478231.jpg)
However, in the absence of stress, the most important role of the p53 family is to regulate differentiation and development. They are involved in development, differentiation and cell response to stress. P63 belongs to the p53 family of transcription factors, together with p53 and p73. However, direct CFs reprogramming is accomplished through the activation of cardiac gene expression but must also be accompanied by complete silencing of the original CFs signature. Several reviews highlight the potential and challenges of this new avenue for cardiac regenerative medicine ( 6). In 2010, was reported that mouse cardiac and dermal fibroblasts could be directly reprogrammed into induced CM-like cells (iCMs) in-vitro by a combination of 3 developmental cardiac transcription factors, Gata4, Mef2c, and Tbx5 ( 5). Therefore, reprogramming CFs into CMs represents a promising and beneficial approach and will be revolutionary for heart regeneration. After myocardial infarction, the fibroblasts expand and constitute the majority of the cells in the infarct zone ( 10, 11). CFs has been identified as an ideal cell source for direct reprogramming into CMs ( 9). Moreover, they have been termed as sentinel cells due to its capacity to respond to an inflammatory stimulus and also to secrete cytokines and chemokines enhancing cardiac inflammation response ( 8). In response to a profibrotic stimulus, CFs predominantly proliferate and synthesize ECM and growth factors, leading to the formation of fibrosis and myocardial remodeling ( 7). Several strategies have been developed in order to get new CMs, including induced pluripotent stem cells (iPSCs) and its differentiation into CMs ( 2, 3) activation of cardiac stem cells or stimulation of CMs to re-enter the cell cycle ( 4) and direct reprogramming or transdifferentiation of cardiac fibroblasts (CFs) to CMs ( 5, 6).ĬFs are fully differentiated mesenchymal cells and they play a key role in extracellular matrix (ECM) homeostasis in the heart. Cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. The very limited regenerative capacity of CMs is the main problem for heart repair.
![cfs to cms cfs to cms](https://pbs.twimg.com/media/FAIf2SWVEAwgGhq.jpg)
Most heart diseases are often accompanied by a severe loss of cardiomyocytes (CMs) and by a pathological remodeling of the heart, culminating in heart failure or even sudden death ( 1).