Embryomics
Encyclopedia
Embryomics is the identification, characterization and study of the diverse cell types which arise during embryogenesis, especially as this relates to the location and developmental history of cells in the embryo. Cell type may be determined according to several criteria: location in the developing embryo
, gene expression as indicated by protein and nucleic acid markers and surface antigens, and also position on the embryogenic tree.
into many cells, which grow in number and migrate to the appropriate locations inside the embryo at appropriate times during development. As the embryo’s cells grow in number and migrate, they also differentiate
into an increasing number of different cell types, ultimately turning into the stable, specialized cell types characteristic of the adult organism. Each of the cells in an embryo contains the same genome
, characteristic of the species(1), but the level of activity of each of the many thousands of gene
s that make up the complete genome varies with, and determines, a particular cell’s type (e.g. neuron, bone cell, skin cell, muscle cell, etc.).
During embryo development (embryogenesis), many cell types are present which are not present in the adult organism. These temporary cells are called progenitor cells, and are intermediate cell types which disappear during embryogenesis by turning into other progenitor cells, or into mature adult somatic cell types, or which disappear due to programmed cell death (apoptosis
).
The entire process of embryogenesis can be described with the aid of two maps: an embryo map, a temporal sequence of 3-dimensional images of the developing embryo, showing the location of cells of the many cell types present in the embryo at a given time, and an embryogenic tree, a diagram showing how the cell types are derived from each other during embryogenesis.
The embryo map is straightforward: It is a sequence of 3-D images, or slices of 3-D images, of the developing embryo which, if viewed rapidly in temporal order, forms a time-lapse view of the growing embryo.
The embryogenic tree is a diagram which shows the temporal development of each of the cell lines in the embryo. When drawn on a piece of paper, this diagram takes the form of a tree, analogous to the evolutionary tree of life
which illustrates the development of life on Earth. However, instead of each branch on this tree representing a species, as in the tree of life, each branch represents a particular cell type present in the embryo at a particular time. And of course, an embryogenic tree covers the gestation
period of weeks or months, instead of billions of years, as in the case of the evolutionary tree of life.
We use human embryogenesis as our referent here, but embryogenesis in other vertebrate species closely follows the same pattern. The egg cell (ovum), after fertilization with a sperm cell, becomes the zygote, represented by the trunk at the very bottom of the tree. This single zygote cell divides in two, three times, forming first a cluster of two-cells, then four-cells, and finally eight-cells. One more cell division brings the number of cells to 16, at which time it is called a morula, instead of a zygote. This ball of 16 cells then reorganizes into a hollow sphere called a blastocyst. As the number of cells grows from 16 to between 40 and 150, the blastocyst differentiates into two layers, an outer sphere of cells called the trophoblast and an inner cell mass called the embryoblast.
The spherical outer cell layer (trophoblast), after implantation in the wall of the uterus, further differentiates and grows to form the placenta.
The cells of the inner cell mass (embryoblast), which are known as human embryonic stem cells (hESCs), will further differentiate to form four structures: the amnion, the yolk sac, the allantois, and the embryo itself. Human embryonic stem cells are pluripotent, that is, they can differentiate into any of the cell types present in the adult human, and into any of the intermediate progenitor cell types that eventually turn into the adult cell lines. hESCs are also immortal, in that they can divide and grow in number indefinitely, without undergoing either differentiation or cellular aging (cellular senescence).
The first differentiation of the hESCs that form the embryo proper, is into three cell types known as the germ layers: the ectoderm, the mesoderm, and the endoderm. The ectoderm eventually forms the skin (including hair and nails), mucous membranes and nervous system. The mesoderm forms the skeleton and muscles, heart and circulatory system, urinary and reproductive systems, and connective tissues inside the body. The endoderm forms the gastrointestinal tract (stomach and intestines), the respiratory tract, and the endocrine system (liver and endocrine glands).
Each cell type is defined by which genes are characteristically active in that cell type. A particular gene in a cell’s genome codes for the production of a particular protein
, that is, when that gene is turned on (active), the protein coded for by that gene is produced and present somewhere in the cell. Production of a particular protein involves the production of a particular mRNA (messenger RNA
) sequence as an intermediate step in protein synthesis. This mRNA is produced by copying process called transcription, from the DNA in the cell’s nucleus. The mRNA so produced travels from the nucleus into the cytoplasm, where it encounters and latches onto ribosomes stuck to the cytoplasmic side of the endoplasmic reticulum. Attachment of the mRNA strand to the ribosome initiates the production of the protein coded for by the mRNA strand. Therefore the profile of active genes in a cell is reflected in the presence or absence of corresponding proteins and mRNA strands in the cell’s cytoplasm, and antigen proteins
present on the cell’s outer membrane. Discovering, determining and classifying cells as to their type therefore involves detecting and measuring the type and amount of specific protein and RNA molecules present in the cells.
In addition, mapping the tree of embryogenesis involves assigning to each specific, identifiable cell type, a particular branch, or place, in the tree. This requires knowing the “ancestry” of each cell type, that is, which cell type preceded it in the development process. This information can be deduced by observing in detail the distribution and placement of cells, by type, in the developing embryo, and by also observing, in cells growing in culture (“in vitro
”) any differentiation events, should they occur for whatever reason, and by other means.
Cells, embryonic cells in particular, are sensitive to the presence or absence of specific chemical molecules in their surroundings. This is the basis for cell signaling
, and during embryogenesis cells “talk to each other” by emitting and receiving signaling molecules. This is how development of the embryo’s structure is organized and controlled. If cells of a particular line have been removed from the embryo and are growing alone in a Petri dish in the lab, and some cell signaling chemicals are put in the growth medium bathing the cells, this can induce the cells to differentiate into a different, “daughter” cell type, mimicking the differentiation process that occurs naturally in the developing embryo. Artificially inducing differentiation in this way can yield clues to the correct placement of a particular cell line in the embryogenic tree, by observing what kind of cell results from inducing the differentiation.
In the laboratory, human embryonic stem cells growing in culture can be induced to differentiate into progenitor cells by exposing the hESCs to chemicals (e.g. protein growth and differentiation factors) present in the developing embryo. The progenitor cells so produced may then be isolated into pure colonies, grown in culture, and then classified according to type and assigned positions in the embryogenic tree. Such purified cultures of progenitor cells may be used in research to study disease processes in vitro, as diagnostic tools, or potentially developed for use in regenerative medicine therapies(2).
. Regenerative medicine involves use of specially grown cells, tissues and organs as therapeutic agents to cure disease and repair injury, and springs from the development of mammalian cloning technology(3). Other medical and surgical methods may use chemicals (pharmaceuticals
) as therapeutic agents, or involve removal of injured or diseased tissue (surgery
), or use inserted tissues or organs (transplant surgery
). Use of transplanted tissue or organs in medicine is not classified as regenerative medicine, because the tissues and organs were not grown specifically for use as therapeutic agents.
Ultimately, one of the goals of regenerative medicine and applied embryomics, is the creation of cells, tissues and organs grown from cells taken from the patient to be treated. This would be accomplished by reprogramming adult stem or somatic cells removed from the patient, so that these cells revert to the pluripotent, embryonic state(4,5,6). These synthetic stem cells would then be grown in culture and differentiated into the appropriate cell type indicated for treating the patient’s disease or injury. The advantages here over current therapies are: elimination of immune rejection accompanying allograft transplantation, creation of a full complement of cells, tissues and organs as needed, and creation of youthful cells, tissues and organs for transplant and rejuvenation
.
Technology for growing cells, tissues and organs for use in regenerative medicine can be developed by using the natural course of development of those cells, tissues and organs during embryogenesis, as a guide. Therefore, detailed knowledge of the complete embryome and the embryogenic tree is key to developing the full potential of regenerative medicine.
Embryomics also includes the application of embryomic data and theory, to the development of practical methods for evaluating, classifying, culturing, purifying, differentiating and manipulating human embryonic cells.
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
, gene expression as indicated by protein and nucleic acid markers and surface antigens, and also position on the embryogenic tree.
The Embryome
There are many cell markers useful in distinguishing, classifying, separating and purifying the numerous cell types present at any given time in a developing organism. These cell markers consist of select RNAs and proteins present inside, and surface antigens present on the surface of, the cells making up the embryo. For any given cell type, these RNA and protein markers reflect the genes characteristically active in that cell type. The catalog of all these cell types and their characteristic markers is known as the organism's embryome. The word is a portmanteau of embryo and genome. “Embryome” may also refer to the totality of the physical cell markers themselves.Embryogenesis
As an embryo develops from a fertilized egg, the single egg cell splitsCell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
into many cells, which grow in number and migrate to the appropriate locations inside the embryo at appropriate times during development. As the embryo’s cells grow in number and migrate, they also differentiate
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
into an increasing number of different cell types, ultimately turning into the stable, specialized cell types characteristic of the adult organism. Each of the cells in an embryo contains the same genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
, characteristic of the species(1), but the level of activity of each of the many thousands of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s that make up the complete genome varies with, and determines, a particular cell’s type (e.g. neuron, bone cell, skin cell, muscle cell, etc.).
During embryo development (embryogenesis), many cell types are present which are not present in the adult organism. These temporary cells are called progenitor cells, and are intermediate cell types which disappear during embryogenesis by turning into other progenitor cells, or into mature adult somatic cell types, or which disappear due to programmed cell death (apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
).
The entire process of embryogenesis can be described with the aid of two maps: an embryo map, a temporal sequence of 3-dimensional images of the developing embryo, showing the location of cells of the many cell types present in the embryo at a given time, and an embryogenic tree, a diagram showing how the cell types are derived from each other during embryogenesis.
The embryo map is straightforward: It is a sequence of 3-D images, or slices of 3-D images, of the developing embryo which, if viewed rapidly in temporal order, forms a time-lapse view of the growing embryo.
The embryogenic tree is a diagram which shows the temporal development of each of the cell lines in the embryo. When drawn on a piece of paper, this diagram takes the form of a tree, analogous to the evolutionary tree of life
Phylogenetic tree
A phylogenetic tree or evolutionary tree is a branching diagram or "tree" showing the inferred evolutionary relationships among various biological species or other entities based upon similarities and differences in their physical and/or genetic characteristics...
which illustrates the development of life on Earth. However, instead of each branch on this tree representing a species, as in the tree of life, each branch represents a particular cell type present in the embryo at a particular time. And of course, an embryogenic tree covers the gestation
Gestation
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....
period of weeks or months, instead of billions of years, as in the case of the evolutionary tree of life.
We use human embryogenesis as our referent here, but embryogenesis in other vertebrate species closely follows the same pattern. The egg cell (ovum), after fertilization with a sperm cell, becomes the zygote, represented by the trunk at the very bottom of the tree. This single zygote cell divides in two, three times, forming first a cluster of two-cells, then four-cells, and finally eight-cells. One more cell division brings the number of cells to 16, at which time it is called a morula, instead of a zygote. This ball of 16 cells then reorganizes into a hollow sphere called a blastocyst. As the number of cells grows from 16 to between 40 and 150, the blastocyst differentiates into two layers, an outer sphere of cells called the trophoblast and an inner cell mass called the embryoblast.
The spherical outer cell layer (trophoblast), after implantation in the wall of the uterus, further differentiates and grows to form the placenta.
The cells of the inner cell mass (embryoblast), which are known as human embryonic stem cells (hESCs), will further differentiate to form four structures: the amnion, the yolk sac, the allantois, and the embryo itself. Human embryonic stem cells are pluripotent, that is, they can differentiate into any of the cell types present in the adult human, and into any of the intermediate progenitor cell types that eventually turn into the adult cell lines. hESCs are also immortal, in that they can divide and grow in number indefinitely, without undergoing either differentiation or cellular aging (cellular senescence).
The first differentiation of the hESCs that form the embryo proper, is into three cell types known as the germ layers: the ectoderm, the mesoderm, and the endoderm. The ectoderm eventually forms the skin (including hair and nails), mucous membranes and nervous system. The mesoderm forms the skeleton and muscles, heart and circulatory system, urinary and reproductive systems, and connective tissues inside the body. The endoderm forms the gastrointestinal tract (stomach and intestines), the respiratory tract, and the endocrine system (liver and endocrine glands).
Mapping the Embryogenic Tree
A primary goal in embryomics is a complete mapping the embryogenic tree: Indentifying each of the cell types present in the developing embryo and placing it in the tree on its proper branch. There is an unknown number, probably thousands, of distinct cell types present in the developing embryo, including progenitor cell lines which are only temporarily present and which disappear either by differentiating into the permanent somatic cell types which make up the tissues of the infant’s body at birth (or into other progenitor cell lines), or by undergoing the programmed cell death process known as apoptosis.Each cell type is defined by which genes are characteristically active in that cell type. A particular gene in a cell’s genome codes for the production of a particular protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, that is, when that gene is turned on (active), the protein coded for by that gene is produced and present somewhere in the cell. Production of a particular protein involves the production of a particular mRNA (messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
) sequence as an intermediate step in protein synthesis. This mRNA is produced by copying process called transcription, from the DNA in the cell’s nucleus. The mRNA so produced travels from the nucleus into the cytoplasm, where it encounters and latches onto ribosomes stuck to the cytoplasmic side of the endoplasmic reticulum. Attachment of the mRNA strand to the ribosome initiates the production of the protein coded for by the mRNA strand. Therefore the profile of active genes in a cell is reflected in the presence or absence of corresponding proteins and mRNA strands in the cell’s cytoplasm, and antigen proteins
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
present on the cell’s outer membrane. Discovering, determining and classifying cells as to their type therefore involves detecting and measuring the type and amount of specific protein and RNA molecules present in the cells.
In addition, mapping the tree of embryogenesis involves assigning to each specific, identifiable cell type, a particular branch, or place, in the tree. This requires knowing the “ancestry” of each cell type, that is, which cell type preceded it in the development process. This information can be deduced by observing in detail the distribution and placement of cells, by type, in the developing embryo, and by also observing, in cells growing in culture (“in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
”) any differentiation events, should they occur for whatever reason, and by other means.
Cells, embryonic cells in particular, are sensitive to the presence or absence of specific chemical molecules in their surroundings. This is the basis for cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
, and during embryogenesis cells “talk to each other” by emitting and receiving signaling molecules. This is how development of the embryo’s structure is organized and controlled. If cells of a particular line have been removed from the embryo and are growing alone in a Petri dish in the lab, and some cell signaling chemicals are put in the growth medium bathing the cells, this can induce the cells to differentiate into a different, “daughter” cell type, mimicking the differentiation process that occurs naturally in the developing embryo. Artificially inducing differentiation in this way can yield clues to the correct placement of a particular cell line in the embryogenic tree, by observing what kind of cell results from inducing the differentiation.
In the laboratory, human embryonic stem cells growing in culture can be induced to differentiate into progenitor cells by exposing the hESCs to chemicals (e.g. protein growth and differentiation factors) present in the developing embryo. The progenitor cells so produced may then be isolated into pure colonies, grown in culture, and then classified according to type and assigned positions in the embryogenic tree. Such purified cultures of progenitor cells may be used in research to study disease processes in vitro, as diagnostic tools, or potentially developed for use in regenerative medicine therapies(2).
Embryomics and Regenerative Medicine
Embryomics is the core science supporting the development of regenerative medicineStem cell treatments
Stem cell treatments are a type of intervention strategy that introduces new cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering...
. Regenerative medicine involves use of specially grown cells, tissues and organs as therapeutic agents to cure disease and repair injury, and springs from the development of mammalian cloning technology(3). Other medical and surgical methods may use chemicals (pharmaceuticals
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
) as therapeutic agents, or involve removal of injured or diseased tissue (surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
), or use inserted tissues or organs (transplant surgery
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
). Use of transplanted tissue or organs in medicine is not classified as regenerative medicine, because the tissues and organs were not grown specifically for use as therapeutic agents.
Ultimately, one of the goals of regenerative medicine and applied embryomics, is the creation of cells, tissues and organs grown from cells taken from the patient to be treated. This would be accomplished by reprogramming adult stem or somatic cells removed from the patient, so that these cells revert to the pluripotent, embryonic state(4,5,6). These synthetic stem cells would then be grown in culture and differentiated into the appropriate cell type indicated for treating the patient’s disease or injury. The advantages here over current therapies are: elimination of immune rejection accompanying allograft transplantation, creation of a full complement of cells, tissues and organs as needed, and creation of youthful cells, tissues and organs for transplant and rejuvenation
Rejuvenation (aging)
Rejuvenation is the hypothetical reversal of the aging process.Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes in order to slow aging...
.
Technology for growing cells, tissues and organs for use in regenerative medicine can be developed by using the natural course of development of those cells, tissues and organs during embryogenesis, as a guide. Therefore, detailed knowledge of the complete embryome and the embryogenic tree is key to developing the full potential of regenerative medicine.
Embryomics also includes the application of embryomic data and theory, to the development of practical methods for evaluating, classifying, culturing, purifying, differentiating and manipulating human embryonic cells.
External links
- CNRS Embryomics Project : reconstructing in space and time the cell lineage tree
- Description of an approach to embryomics at the Bioemergences website
- GenePaint.org digital atlas of gene expression patterns in the mouse
- A database containing gene expression information in the mouse
- The journal Regenerative Medicine has papers showing applications of regenerative medicine to treating various diseases
- The California Institute for Regenerative Medicine website has information on development of stem cell based therapies.
- WormWeb.org: Interactive Visualization of the C. elegans Cell lineage - Visualize the entire cell lineage tree of the nematode C. elegans