Cellular specialization (differentiation) (video) | Khan Academy
Cell specialization, also known as cell differentiation, is the process by to replace cells that are worn out in the bone marrow, brain, heart and. In multicellular organisms each cell performs specific functions, this is known as specialisation of the cell. However, sometimes cells undergo some changes. We explored the relationship between duplication events, the time at which they to illustrate how differentiation of expression contributes to specialization of .. of the total number of proteins expressed in the tissue) is observed in the brain.
One aspect of metazoan genome evolution is the emergence of metazoan-specific genes. The contribution of metazoan-specific genes to tissue differentiation was recently demonstrated in a few studies that characterized the tendency of such genes to be specifically expressed in mammalian tissues [ 1 - 3 ].How Cells Become Specialized
However, tissue-specific genes are not solely metazoan specific. Pre-metazoan genes genes that are assumed to have been present in the genome of the unicellular ancestor of animalsdespite their general tendency to be globally expressed, are in many cases tissue specific [ 1 ].
In some cases in which a pre-metazoan gene is specifically expressed, a duplicate copy of the gene maintains a global expression pattern for examples, see [ 45 ].
Gene duplication events therefore provide an additional dimension when studying the relationship between the phyletic age of a gene and its expression breadth. More broadly, gene duplication is a dominant aspect in the evolution of metazoan genomes, and therefore it is important to understand its contribution to tissue differentiation [ 67 ].
Gene duplication events have been suggested to contribute to the attainment of the complex body organization in metazoan species [ 6 ]. A possible mechanism through which gene duplication can contribute to tissue differentiation is described in the recent model of subfunctionalization [ 8 ].
According to this model, two daughter genes can accumulate degenerative mutations, resulting in the division of the ancestral function, and hence promote the retention of both duplicate copies in the genome. Division of the expression of the ancestral gene between its daughter duplicates, through the accumulation of mutations in the promoter region, is one mode of function division. Several examples for subfunctionalization of expression were reported for individual genes [ 7910 ].
The findings from several studies that used microarray expression information to explore several aspects of the relationship between gene duplication and expression divergence are consistent with these predicted from the subfunctionalization model. Expression divergence between duplicate genes was shown to increase with evolutionary time when studying both temporal differentiation modes in yeast [ 11 ] and spatial human tissues [ 12 ] and plant tissues [ 13 ] expression divergence patterns, where the divergence of expression occurs relatively shortly after the duplication event.
Duplication events of mammalian genes tend to lead toward a tissue-specific expression pattern of the duplicated genes [ 14 ]. By using expression information from various mouse tissues, we explore several aspects of the relationship between duplication events and specialization of expression that have not yet been characterized. First, we studied the relationship between duplication events and the expression breadth of the duplicated genes.
Previous analysis [ 14 ] has shown a general trend toward increased tissue specificity as family size increases.
Mechanisms[ edit ] Mechanisms of cellular differentiation. Each specialized cell type in an organism expresses a subset of all the genes that constitute the genome of that species. Each cell type is defined by its particular pattern of regulated gene expression.
Cell differentiation is thus a transition of a cell from one cell type to another and it involves a switch from one pattern of gene expression to another. Cellular differentiation during development can be understood as the result of a gene regulatory network.
A regulatory gene and its cis-regulatory modules are nodes in a gene regulatory network; they receive input and create output elsewhere in the network. However, an alternative view has been proposed recently. Based on stochastic gene expression, cellular differentiation is the result of a Darwinian selective process occurring among cells.
In this frame, protein and gene networks are the result of cellular processes and not their cause.
Explanation of Cell Specialization | Sciencing
Cellular Darwinism An overview of major signal transduction pathways. A few evolutionarily conserved types of molecular processes are often involved in the cellular mechanisms that control these switches.
The major types of molecular processes that control cellular differentiation involve cell signaling. Many of the signal molecules that convey information from cell to cell during the control of cellular differentiation are called growth factors.
Although the details of specific signal transduction pathways vary, these pathways often share the following general steps. A ligand produced by one cell binds to a receptor in the extracellular region of another cell, inducing a conformational change in the receptor.
The shape of the cytoplasmic domain of the receptor changes, and the receptor acquires enzymatic activity. The receptor then catalyzes reactions that phosphorylate other proteins, activating them.
A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in the target cell. Asymmetric cell divisions can occur because of asymmetrically expressed maternal cytoplasmic determinants or because of signaling. A well-studied example of pattern formation by asymmetric divisions is body axis patterning in Drosophila.
RNA molecules are an important type of intracellular differentiation control signal. The molecular and genetic basis of asymmetric cell divisions has also been studied in green algae of the genus Volvoxa model system for studying how unicellular organisms can evolve into multicellular organisms.
The size of the cell at the end of all cell divisions determines whether it becomes a specialized germ or somatic cell. Epigenetics in stem cell differentiation Since each cell, regardless of cell type, possesses the same genomedetermination of cell type must occur at the level of gene expression. While the regulation of gene expression can occur through cis- and trans-regulatory elements including a gene's promoter and enhancersthe problem arises as to how this expression pattern is maintained over numerous generations of cell division.
As it turns out, epigenetic processes play a crucial role in regulating the decision to adopt a stem, progenitor, or mature cell fate. This section will focus primarily on mammalian stem cells. In systems biology and mathematical modeling of gene regulatory networks, cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence the attractor can be an equilibrium point, limit cycle or strange attractor or oscillatory.
A clear answer to this question can be seen in the paper by Lister R, et al. As induced pluripotent stem cells iPSCs are thought to mimic embryonic stem cells in their pluripotent properties, few epigenetic differences should exist between them.
Cellular differentiation - Wikipedia
To test this prediction, the authors conducted whole-genome profiling of DNA methylation patterns in several human embryonic stem cell ESCiPSC, and progenitor cell lines. Lister R, et al. In addition, somatic cells possessed minimal levels of cytosine methylation in non-CG dinucleotides, while induced pluripotent cells possessed similar levels of methylation as embryonic stem cells, between 0.
However, upon examining methylation patterns more closely, the authors discovered regions of differential CG dinucleotide methylation between at least one ES or iPS cell line.
Two conclusions are readily apparent from this study. First, epigenetic processes are heavily involved in cell fate determination, as seen from the similar levels of cytosine methylation between induced pluripotent and embryonic stem cells, consistent with their respective patterns of transcription.
Second, the mechanisms of de-differentiation and by extension, differentiation are very complex and cannot be easily duplicated, as seen by the significant number of differentially methylated regions between ES and iPS cell lines.
Now that these two points have been established, we can examine some of the epigenetic mechanisms that are thought to regulate cellular differentiation.
Mechanisms of epigenetic regulation[ edit ] Pioneering factors Oct4, Sox2, Nanog [ edit ] Three transcription factors, OCT4, SOX2, and NANOG — the first two of which are used in induced pluripotent stem cell iPSC reprogramming, along with Klf4 and c-Myc — are highly expressed in undifferentiated embryonic stem cells and are necessary for the maintenance of their pluripotency.
While highly expressed, their levels require a precise balance to maintain pluripotency, perturbation of which will promote differentiation towards different lineages based on how the gene expression levels change.
Differential regulation of Oct-4 and SOX2 levels have been shown to precede germ layer fate selection. Similarly, Increased levels of Sox2 and decreased levels of Oct4 promote differentiation towards a neural ectodermal fate, with Sox2 inhibiting differentiation towards a mesendodermal fate.
Regardless of the lineage cells differentiate down, suppression of NANOG has been identified as a necessary prerequisite for differentiation.
Trithorax group proteins TrxG [ edit ] Alternately, upon receiving differentiation signals, PcG proteins are recruited to promoters of pluripotency transcription factors.
PcG-deficient ES cells can begin differentiation but cannot maintain the differentiated phenotype. Consistently, DNA methylation-deficient embryonic stem cells rapidly enter apoptosis upon in vitro differentiation. In particular, it is important to know whether a nucleosome is covering a given genomic binding site or not.
This can be determined using a chromatin immunoprecipitation ChIP assay. The epigenetic processes of histone methylation and acetylation, and their inverses demethylation and deacetylation primarily account for these changes. The effects of acetylation and deacetylation are more predictable. An acetyl group is either added to or removed from the positively charged Lysine residues in histones by enzymes called histone acetyltransferases or histone deacteylasesrespectively.
The acetyl group prevents Lysine's association with the negatively charged DNA backbone. Methylation is not as straightforward, as neither methylation nor demethylation consistently correlate with either gene activation or repression.
However, certain methylations have been repeatedly shown to either activate or repress genes.