Transdifferentiation
Encyclopedia
Transdifferentiation in biology takes place when a non-stem cell
transforms into a different type of cell, or when an already differentiated
stem cell creates cells outside its already established differentiation path. Transdifferentiation is a type of metaplasia
, which includes all cell fate switches, including the interconversion of stem cells.
Transdifferentiation takes place in nature in a few specific cases. For example, in salamander
s and chickens when the lens of the eye is removed, cells of the iris
turn into lens cells. Still, such naturally occurring cases, or even ones created in the laboratory are rare.
Until recently, biologists were not much interested in the matter, believing it to be something without much practical consequence. However, around 2001 biologist Philippe Collas published results that seem to show that some cells can be transformed into other types of cells.
The scientists at the biotechnology firm Nucleotech demonstrated the in vitro
reprogramming of fibroblast
s by first creating tiny pores in the cells through reversible permeabilization and then exposing the permeabilized cells to an extract derived from immune cells containing a mixture of regulatory factors but no genetic material. The reprogrammed cells were removed from the extract, resealed and grown in a culture. As a result, in less than an hour's time the regulatory factors were actively taken up by the nucleus causing the fibroblast cells to express molecules and functions characteristic to immune cells while down-regulating the original cells' typically expressed genes.
Many biologists are still skeptical. They say the transdifferentiation that Collas has shown are not complete - the cells did switch on some of the genes that would be used in their 'new' type but not in their 'old', but they did not switch off all of their old genes. It is still an open question whether transdifferentiation could cause a complete change of cell type, and whether such a change would remain active after the cell has been re-implanted in the body.
Although transdifferentiation is rare in vertebrates, it occurs in the fetal
development of the oesophagus, when the tunica muscularis which is composed of smooth muscle transdifferentiates into skeletal muscle across:
During this process, smooth muscle cells transform back into myoblasts, then line up and fuse to form myotubes which then become cylindrical skeletal muscle fibers.
Evidence for transdifferentiation in adult humans is given by Barrett's metaplasia in which epithelieal cells of the oesophagus switch to intestinal mucin-secreting goblet cells. Barrett's metaplasia predisposes people to adenocarcinoma
, with an 80% mortality rate.
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
transforms into a different type of cell, or when an already differentiated
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...
stem cell creates cells outside its already established differentiation path. Transdifferentiation is a type of metaplasia
Metaplasia
Metaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...
, which includes all cell fate switches, including the interconversion of stem cells.
Transdifferentiation takes place in nature in a few specific cases. For example, in salamander
Salamander
Salamander is a common name of approximately 500 species of amphibians. They are typically characterized by a superficially lizard-like appearance, with their slender bodies, short noses, and long tails. All known fossils and extinct species fall under the order Caudata, while sometimes the extant...
s and chickens when the lens of the eye is removed, cells of the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
turn into lens cells. Still, such naturally occurring cases, or even ones created in the laboratory are rare.
Until recently, biologists were not much interested in the matter, believing it to be something without much practical consequence. However, around 2001 biologist Philippe Collas published results that seem to show that some cells can be transformed into other types of cells.
The scientists at the biotechnology firm Nucleotech demonstrated the 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...
reprogramming of fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s by first creating tiny pores in the cells through reversible permeabilization and then exposing the permeabilized cells to an extract derived from immune cells containing a mixture of regulatory factors but no genetic material. The reprogrammed cells were removed from the extract, resealed and grown in a culture. As a result, in less than an hour's time the regulatory factors were actively taken up by the nucleus causing the fibroblast cells to express molecules and functions characteristic to immune cells while down-regulating the original cells' typically expressed genes.
Many biologists are still skeptical. They say the transdifferentiation that Collas has shown are not complete - the cells did switch on some of the genes that would be used in their 'new' type but not in their 'old', but they did not switch off all of their old genes. It is still an open question whether transdifferentiation could cause a complete change of cell type, and whether such a change would remain active after the cell has been re-implanted in the body.
Although transdifferentiation is rare in vertebrates, it occurs in the fetal
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
development of the oesophagus, when the tunica muscularis which is composed of smooth muscle transdifferentiates into skeletal muscle across:
- The entire wall of the oesophagus (ruminantRuminantA ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first compartment of the stomach, principally through bacterial actions, then regurgitating the semi-digested mass, now known as cud, and chewing it again...
s, dogDogThe domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
) - The entire wall excluding the stomach junction (pigPigA pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
) or - The cranial 2/3 of the oesophageal wall (catCatThe cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
, horseHorseThe horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
).
During this process, smooth muscle cells transform back into myoblasts, then line up and fuse to form myotubes which then become cylindrical skeletal muscle fibers.
Evidence for transdifferentiation in adult humans is given by Barrett's metaplasia in which epithelieal cells of the oesophagus switch to intestinal mucin-secreting goblet cells. Barrett's metaplasia predisposes people to adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
, with an 80% mortality rate.
See also
- EpigeneticsEpigeneticsIn biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
- Turritopsis nutriculaTurritopsis nutriculaTurritopsis nutricula, the immortal jellyfish, is a hydrozoan whose medusa, or jellyfish, form can revert to the polyp stage after becoming sexually mature. It is the only known case of a metazoan capable of reverting completely to a sexually immature, colonial stage after having reached sexual...
(Biologically immortal jellyfish via transdifferentiation)