The principles that govern Cell phenotype definition
Differentiation of the various cell types present in multicellular organisms requires the establishment of spatiotemporal patterns of gene expression during development. Transcription of eukaryotic genes is an exceedingly intricate process that requires the precise orchestration of a complex set of interactions among a myriad of proteins and DNA sequences. 5 Tissue-specific transcription factors primarily act to define the phenotype of the cell. The power of a single transcription factor to alter cell fate is often minimal. When multiple transcription factors cooperate synergistically it potentiates their ability to induce changes in cell fate. By contrast, transcription factor function is often dispensable in the maintenance of cell phenotype. Transcription factor networks play collaboratively regulating stem cell fate and differentiation. 1 Cellular identity as defined through morphology and function emerges from intracellular signaling networks that communicate between cells. 2 Intercellular communication results in novel dynamical solutions and correct cell differentiation. Cells require encapsulation to spatially organize their chemical constituents. Under such confinement, they can control the flow of matter and energy, thereby maintaining themselves in entropy‐dissipating non‐equilibrium conditions. This enables information to be concentrated in cells in a form of self‐organizing chemical activity patterns. The cells continuously adjust these internal states to allow for robustness in identity under changing external conditions, especially to unfamiliar changes for which the regulatory program has been set up and programmed in advance. Distinct biochemical manifestations of this information pool reflect proteome plasticity: In multicellular organisms, all cells contain nearly identical copies of the genome but exhibit drastically different phenotypes. This principle also accounts for efficient adaptation as well as short timescales and implicitly incorporates the pre-programmed ( front loaded) instructional aspect of biological systems. Cells thereby define a wider dynamical domain in which they can interact with their environment to generate and maintain their identity, a process reminiscent to cognition.
Autopoiesis and Cognition—the realization of the living, H. Maturana and F. Varela:
“… units of interactions, they exist in ambience. From a purely biological point of view, they can not be understood independently of the part of the ambience with which they interact".
Cell cognition can be understood as a process driven by structural, bidirectional causal organism-environment relations that are grounded in biosemiotics, front-loaded adaptive mechanisms based on genetic and epigenetic codes, information coding and information transmission in living systems. The concept of cellular cognition relates to the characteristics of the immune system within a living organism in order to encompass its properties of recognition, learning, memory, and self/non‐self discrimination. Moreover, a system is cognitive if and only if sensory inputs serve to trigger actions in a specific way, so as to satisfy a viability constraint.
During development, a single, totipotent cell divides repeatedly and can give rise to a few billion, or even trillion cells, which differentiate into a few hundred different cell types. Differentiation is the process by which a cell changes phenotype and becomes increasingly specialized. Cell phenotypes are defined by particular combinations of genes expressed in a cell type-dependent manner. The selection of these combinations is mainly driven by cell type-specific transcription factors (TFs), which in turn are regulated by other TFs that integrate and respond to extracellular signals in order to maintain cell phenotype. Thus, TFs form a network in which each TF is reciprocally regulated to maintain its balanced expression. A TF network often forms part of a gene regulatory network. Gene regulatory networks are divided into functional subcircuits.
The modular components, or subcircuits, of developmental gene regulatory networks (GRNs) execute specific developmental functions, such as the specification of cell identity. 3 Developmental gene regulatory networks (GRNs) provide the specific causal links between genomic regulatory sequences and the processes of development. They consist of the regulatory and signaling genes that drive any given process of development and the functional interactions among them. The design features of the GRN directly explain why the events of a given process of development occur; for example, why a given set of cells becomes specified to a given fate, why it emits particular signals to adjacent cells, and why it differentiates in a given direction. The architecture of a GRN is mandated by the cis-regulatory sequences a of the enhancers that control each gene of the network. These sequences determine what inputs affect expression of each gene, and how these inputs operate in a combinatorial fashion.
a Cis-regulatory elements (CREs) are regions of non-coding DNA which regulate the transcription of neighbouring genes. CREs are vital components of genetic regulatory networks, which in turn control morphogenesis, the development of anatomy, and other aspects of embryonic development 4
1. http://dev.biologists.org/content/145/6/dev157420
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331751/
3. http://www.pnas.org/content/105/51/20063
4. https://en.wikipedia.org/wiki/Cis-regulatory_element
5. http://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175006/
Differentiation of the various cell types present in multicellular organisms requires the establishment of spatiotemporal patterns of gene expression during development. Transcription of eukaryotic genes is an exceedingly intricate process that requires the precise orchestration of a complex set of interactions among a myriad of proteins and DNA sequences. 5 Tissue-specific transcription factors primarily act to define the phenotype of the cell. The power of a single transcription factor to alter cell fate is often minimal. When multiple transcription factors cooperate synergistically it potentiates their ability to induce changes in cell fate. By contrast, transcription factor function is often dispensable in the maintenance of cell phenotype. Transcription factor networks play collaboratively regulating stem cell fate and differentiation. 1 Cellular identity as defined through morphology and function emerges from intracellular signaling networks that communicate between cells. 2 Intercellular communication results in novel dynamical solutions and correct cell differentiation. Cells require encapsulation to spatially organize their chemical constituents. Under such confinement, they can control the flow of matter and energy, thereby maintaining themselves in entropy‐dissipating non‐equilibrium conditions. This enables information to be concentrated in cells in a form of self‐organizing chemical activity patterns. The cells continuously adjust these internal states to allow for robustness in identity under changing external conditions, especially to unfamiliar changes for which the regulatory program has been set up and programmed in advance. Distinct biochemical manifestations of this information pool reflect proteome plasticity: In multicellular organisms, all cells contain nearly identical copies of the genome but exhibit drastically different phenotypes. This principle also accounts for efficient adaptation as well as short timescales and implicitly incorporates the pre-programmed ( front loaded) instructional aspect of biological systems. Cells thereby define a wider dynamical domain in which they can interact with their environment to generate and maintain their identity, a process reminiscent to cognition.
Autopoiesis and Cognition—the realization of the living, H. Maturana and F. Varela:
“… units of interactions, they exist in ambience. From a purely biological point of view, they can not be understood independently of the part of the ambience with which they interact".
Cell cognition can be understood as a process driven by structural, bidirectional causal organism-environment relations that are grounded in biosemiotics, front-loaded adaptive mechanisms based on genetic and epigenetic codes, information coding and information transmission in living systems. The concept of cellular cognition relates to the characteristics of the immune system within a living organism in order to encompass its properties of recognition, learning, memory, and self/non‐self discrimination. Moreover, a system is cognitive if and only if sensory inputs serve to trigger actions in a specific way, so as to satisfy a viability constraint.
During development, a single, totipotent cell divides repeatedly and can give rise to a few billion, or even trillion cells, which differentiate into a few hundred different cell types. Differentiation is the process by which a cell changes phenotype and becomes increasingly specialized. Cell phenotypes are defined by particular combinations of genes expressed in a cell type-dependent manner. The selection of these combinations is mainly driven by cell type-specific transcription factors (TFs), which in turn are regulated by other TFs that integrate and respond to extracellular signals in order to maintain cell phenotype. Thus, TFs form a network in which each TF is reciprocally regulated to maintain its balanced expression. A TF network often forms part of a gene regulatory network. Gene regulatory networks are divided into functional subcircuits.
The modular components, or subcircuits, of developmental gene regulatory networks (GRNs) execute specific developmental functions, such as the specification of cell identity. 3 Developmental gene regulatory networks (GRNs) provide the specific causal links between genomic regulatory sequences and the processes of development. They consist of the regulatory and signaling genes that drive any given process of development and the functional interactions among them. The design features of the GRN directly explain why the events of a given process of development occur; for example, why a given set of cells becomes specified to a given fate, why it emits particular signals to adjacent cells, and why it differentiates in a given direction. The architecture of a GRN is mandated by the cis-regulatory sequences a of the enhancers that control each gene of the network. These sequences determine what inputs affect expression of each gene, and how these inputs operate in a combinatorial fashion.
a Cis-regulatory elements (CREs) are regions of non-coding DNA which regulate the transcription of neighbouring genes. CREs are vital components of genetic regulatory networks, which in turn control morphogenesis, the development of anatomy, and other aspects of embryonic development 4
1. http://dev.biologists.org/content/145/6/dev157420
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331751/
3. http://www.pnas.org/content/105/51/20063
4. https://en.wikipedia.org/wiki/Cis-regulatory_element
5. http://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175006/
