Waddington diagram illustrate the various developmental pathways which help in pathways development of cell towards differentiation. The diagram proposed by him depicts an scenario of mountains, valleys, and pools as a representation for cell development. In the picture, the marbles and stones reside on a mountain represent as undifferentiated cells. During differentiation or division, it seems that these stones, marbles move down towards the more stable and energized valleys that cause them to come to rest as differentiated and new cell.
Similarly, his vision through this is that like stones and marbles become stable after reaching the stable position, in human body cells also undergo differentiation to attain energetic stable position. He made an assumption that it is difficult to move back the distinct cell into their original position back. The approach of Waddington is stable and is likely to be successful as he realized that the inheritance characteristics determine the forms of development and plasticity. The Waddington concept is relevant to many biologists in past and will be in future as it determine the fate of development and also highlights the epigenetic marking of DNA, its associated chromatin, genes and proteins.
During differentiation, when cell received its final cell fate the chromatin undergo changes. Chromatin undergoes changes structurally during final cell fate development. The histone proteins present inside the cell responsible for arranging the chromatin modeling and make it to undergo changes during post translational modification. These changes alter the chromatin packaging inside and affect the overall structure of chromatin. Post transcriptional modification of histone protein occurs which causes the chromatin structure to change. The covalent modifications of nucleotide and nucleosides influence the transcriptional program.
These changes further cause a huge impact on the cellular behavior and cell fate. Moreover, the transcriptional factors and their mediators have a key role in instructing the specific gene expression program. The chromatin modification can occur due to presence of various chromatin institutions such as erasers, writers, and readers. These techniques interfere with the transcription factor complexes and cause the chromatin remodeling in terms of the fate of cell. Activities which are associated with the chromatin changes are DNA methylation, histone modification, post translational modification and chromatin acetylation
The efficiency of conversion of differentiated cell back to pluripotent is inefficient. The cell once differentiated cannot be reprogram into its original phase. The nuclear reprogramming rejuvenates the somatic cell through editing the epigenetic memories or developing the condition responsible for pluripotency. The revised construction of cell is required to make a cell again a pluripotent. However, the reprograming of any cell can induce the plutriopotecny through transcription factors. But the efficiency of reprogramming of cell to pluripotent is very less. The reason of this lower efficiency is that it is very difficult to maintain the stochastic events to continue the reprograming, remodeling and regenerating. During differentiation various changes epigenetic occur such as DNA methylation, histone modification, and chromatin acetylation.
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