cell lineage
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Cell lineage denotes the developmental history of a tissue or organ from the fertilized embryo. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses, this starts with the originator cells and finishing with a mature cell that can no longer divide. This type of lineage can be studied by marking a cell (with fluorescent molecules or other traceable markers) and following its progeny after cell division. Some organisms, such as ''C. elegans'', have a predetermined pattern of cell progeny and the adult male will always consist of 1031 cells, this is because cell division in ''C. elegans'' is genetically determined and known as
eutely Eutelic organisms have a fixed number of somatic cells when they reach maturity, the exact number being relatively constant for any one species. This phenomenon is also referred to as cell constancy. Development proceeds by cell division until matur ...
. This causes the cell lineage and cell fate to be highly correlated. Other organisms, such as humans, have variable lineages and somatic cell numbers.


''C. elegans'': model organism

As one of the first pioneers of cell lineage, in the 1960s Dr. Sydney Brenner first began observing cell differentiation and succession in the nematode ''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
''. Dr. Brenner chose this organism due to its transparent body, quick reproduction, ease of access, and small size which made it ideal for following cell lineage under a microscope. By 1976, Dr. Brenner and his associate, Dr. John Sulston, had identified part of the cell lineage in the developing nervous system of ''C. elegans''. Initial results showed that the nematode was eutelic (each individual experiences the same differentiation pathways), however work by Sulston and Richard Horvitz showed that several cells necessary for reproduction differentiate after hatching. These cells include vulval cells as well as muscle and neurons. This research also led to the initial observations of programmed cell death, or apoptosis. After mapping various sections of the ''C. elegans''' cell lineage, Dr. Brenner and his associates were able to piece together the first complete and reproducible
fate map Fate mapping is a method used in developmental biology to study the embryonic origin of various adult tissues and structures. The "fate" of each cell or group of cells is mapped onto the embryo, showing which parts of the embryo will develop in ...
of cell lineage. They later received the 2002 Nobel prize for their work in genetic regulation of organ development and programmed cell death. Being that ''c.elegans'' are hermaphrodites, there consist of both male and female organs, where they store sperm and are able to self fertilize. ''C. elegans'' contain 302 neurons and 959 somatic cells, where they begin with 1031, where 72 undergo apoptosis which is programmed cell death. This makes the ''c.elegan''a model organism for studying cell lineage, and being able to observe the cell divisions due to their transparent phenotype.


History of cell lineage

One of the first studies of cell lineages took place in the 1870s by Whitman who studied cleavage patterns in leeches and small invertebrates. He found that some groups, such as nematode worms and ascidians form a pattern of cell division which is identical between individuals and invariable. This high correlation between cell lineage and cell fate was thought to be determined by segregating factors within the dividing cells. Other organisms had stereotyped patterns of cell division and produced sublineages which were the progeny of particular precursor cells. These more variable cell fates are thought to be due to the cells' interaction with the environment. Due to new breakthroughs in tracking cells with greater accuracy, this aided the biological community since a variety of colors are now used in showing the original cells and able to track easily. These colors are fluorescent and marked on the proteins by administering injections to trace such cells.


Techniques of fate mapping

Cell lineage can be determined by two methods, either through direct observation or through clonal analysis. During the early 19th century direct observation was used however it was highly limiting as only small transparent samples could be studied. With the invention of the confocal microscope this allowed larger more complicated organisms to be studied. Perhaps the most popular method of cell
fate mapping Fate mapping is a method used in developmental biology to study the embryonic origin of various adult tissues and structures. The "fate" of each cell or group of cells is mapped onto the embryo, showing which parts of the embryo will develop into ...
in the genetic era is through site-specific recombination mediated by the Cre-Lox or FLP-FRT systems. By utilizing the Cre-Lox or FLP-FRT recombination systems, a reporter gene (usually encoding a fluorescent protein) is activated and permanently labels the cell of interest and its offspring cells, thus the name cell lineage tracing. With the system, researchers could investigate the function of their favorite gene in determining cell fate by designing a genetic model where within a cell one recombination event is designed for manipulating the gene of interest and the other recombination event is designed for activating a reporter gene. One minor issue is that the two recombination events may not occur simultaneously thus the results need to be interpreted with caution. Furthermore, some fluorescent reporters have such an extremely low recombination threshold that they may label cell populations at undesired time-points in the absence of induction. More recently, researchers have begun using synthetic biology approaches and the
CRISPR CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacte ...
/
Cas9 Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...
system to engineer new genetic systems that enable cells to autonomously record lineage information in their own genome. These systems are based on engineered, targeted mutation of defined genetic elements. By generating new, random genomic alterations in each cell generation these approaches facilitate reconstruction of lineage trees. These approaches promise to provide more comprehensive analysis of lineage relationships in model organisms. Computational tree reconstruction methods are also being developed for datasets generated by such approaches.


Early developmental asymmetries

In humans after
fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
, the
zygote A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicellula ...
divides into two cells.
Somatic mutation A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline mutatio ...
s that arise directly after the formation of the zygote, as well as later in development, can be used as markers to trace cell lineages throughout the body. Beginning with cleavages of the zygote, lineages were observed to contribute unequally to
blood cell A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), ...
s. As much as 90% of blood cells were found to be derived from just one of the first two
blastomere In biology, a blastomere is a type of cell produced by cell division (cleavage) of the zygote after fertilization; blastomeres are an essential part of blastula formation, and blastocyst formation in mammals. Human blastomere characteristics In ...
s. In addition, normal development may result in unequal characteristics of symmetrical organs, such as between the left and right frontal and occipital
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
. It was proposed that the efficiency of DNA repair contributes to lineage imbalance, as additional time spent by a cell on
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
may decrease proliferation rate.


References

{{reflist Cell biology