Transdifferentiation, also known as lineage reprogramming, is the process in which one mature
somatic cell
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
is transformed into another mature somatic cell without undergoing an intermediate
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
state or progenitor cell type.
It is a type of
metaplasia
Metaplasia ( gr, "change in form") is the transformation of one differentiated cell type to another differentiated cell type. The change from one type of cell to another may be part of a normal maturation process, or caused by some sort of abno ...
, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and
drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.
Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...
and in the future may include
gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
and
regenerative medicine
Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...
.
The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in
silk moth
The domestic silk moth (''Bombyx mori''), is an insect from the moth family Bombycidae. It is the closest relative of ''Bombyx mandarina'', the wild silk moth. The silkworm is the larva or caterpillar of a silk moth. It is an economically imp ...
s undergoing
metamorphosis
Metamorphosis is a biological process by which an animal physically develops including birth or hatching, involving a conspicuous and relatively abrupt change in the animal's body structure through cell growth and differentiation. Some inse ...
.
Discovery
Davis et al. 1987 reported the first instance (sight) of transdifferentiation where a cell changed from one adult cell type to another. Forcing mouse embryonic
fibroblast
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s to express
MyoD
MyoD, also known as myoblast determination protein 1, is a protein in animals that plays a major role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins know ...
was found to be
sufficient
In logic and mathematics, necessity and sufficiency are terms used to describe a conditional or implicational relationship between two statements. For example, in the conditional statement: "If then ", is necessary for , because the truth of ...
to turn those cells into
myoblast
Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development.
Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development of ...
s.
Natural examples
The only known instances where adult cells change directly from one lineage to another occurs in the species ''
Turritopsis dohrnii
''Turritopsis dohrnii'', also known as the immortal jellyfish, is a species of small, biologically immortal jellyfish found worldwide in temperate to tropic waters. It is one of the few known cases of animals capable of reverting completely to ...
(''which is also known as the immortal jellyfish) and ''
Turritopsis Nutricula
''Turritopsis nutricula'' is a small hydrozoan that once reaching adulthood, can transfer its cells back to childhood. This adaptive trait likely evolved in order to extend the life of the individual. Several different species of the genus ''Tur ...
'' (the
protozoan
Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
which makes the immortal jellyfish immortal). Rather, cells dedifferentiate and then redifferentiate into the cell type of interest. In
newt
A newt is a salamander in the subfamily Pleurodelinae. The terrestrial juvenile phase is called an eft. Unlike other members of the family Salamandridae, newts are semiaquatic, alternating between aquatic and terrestrial habitats. Not all aqua ...
s when the eye lens is removed, pigmented
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells de-differentiate and then redifferentiate into the lens cells. Vincenzo Colucci described this phenomenon in 1891 and Gustav Wolff described the same thing in 1894; the priority issue is examined in Holland (2021).
In the pancreas, it has been demonstrated that alpha cells can spontaneously switch fate and transdifferentiate into beta cells in both healthy and diabetic human and mouse
pancreatic islets
The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...
. While it was previously believed that
oesophageal
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
cells were developed from the transdifferentiation of smooth muscle cells, that has been shown to be false.
Induced and therapeutic examples
The first example of functional transdifferentiation has been provided by Ferber et al. by inducing a shift in the developmental fate of cells in the liver and converting them into '
pancreatic
The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...
beta-cell
Beta cells (β-cells) are a type of cell (biology), cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and fun ...
-like' cells. The cells induced a wide, functional and long-lasting transdifferentiation process that reduced the effects of
hyperglycemia
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
in diabetic mice.
[Sarah Ferber, Amir Halkin, Hofit Cohen, Idit Ber, Yulia Einav, Iris Goldberg, Iris Barshack, Rhona Seijffers, Juri Kopolovic, Nurit Kaiser & Avraham Karasik (2000) -]
Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia
Moreover, the trans-differentiated beta-like cells were found to be resistant to the
autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
attack that characterizes
type 1 diabetes
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
.
The second step was to undergo transdifferentiation in human specimens. By transducing liver cells with a single gene, Sapir et al. were able to induce human liver cells to transdifferentiate into human beta cells.
[Tamar Sapir, Keren Shternhall, Irit Meivar-Levy, Tamar Blumenfeld, Hamutal Cohen, Ehud Skutelsky, Smadar Eventov-Friedman, Iris Barshack, Iris Goldberg, Sarah Pri-Chen, Lya Ben-Dor, Sylvie Polak-Charcon, Avraham Karasik, Ilan Shimon, Eytan Mor, and Sarah Ferber (2005]
Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells
/ref>
This approach has been demonstrated in mice, rat, xenopus
''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...
and human tissues (Al-Hasani et al., 2013).
Schematic model of the hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
-to-beta cell transdifferentiation process. Hepatocytes are obtained by liver biopsy from diabetic patient, cultured and expanded ex vivo
''Ex vivo'' (Latin: "out of the living") literally means that which takes place outside an organism. In science, ''ex vivo'' refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal ...
, transduced with a PDX1
PDX1 (pancreatic and duodenal homeobox 1), also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster.Brooke, N. M., Garcia-Fernàndez, J., & Holland, P. W. (1998). The ParaHox gene cluster is an evolutionary si ...
virus, transdifferentiated into functional insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
-producing beta cells, and transplanted back into the patient.
Granulosa
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, a ...
and theca cells
In biology, a theca (plural thecae) is a sheath or a covering.
Botany
In botany, the theca is related to plant's flower anatomy. The theca of an angiosperm consists of a pair of microsporangia that are adjacent to each other and share a commo ...
in the ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
of adult female mice can transdifferentiate to Sertoli
Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimul ...
and Leydig cell
Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
s via induced knockout of the FOXL2
Forkhead box protein L2 is a protein that in humans is encoded by the ''FOXL2'' gene.
Function
FOXL2 (OMIM 605597) is a transcription factor belonging to the forkhead box (FOX) superfamily, characterized by the forkhead box/winged-helix DNA-bi ...
gene. Similarly, Sertoli cells in the testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
of adult male mice can transdifferentiate to granulosa cells via induced knockout of the DMRT1
Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the ''DMRT1'' gene.
Function
DMRT1 is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cells ...
gene.
Methods
Lineage-instructive approach
In this approach, transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s from progenitor cell
A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...
s of the target cell type are transfected
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to desc ...
into a somatic cell to induce transdifferentiation. There exists two different means of determining which transcription factors to use: by starting with a large pool and narrowing down factors one by one or by starting with one or two and adding more. One theory to explain the exact specifics is that ectopic Transcriptional factors direct the cell to an earlier progenitor state and then redirects it towards a new cell type. Rearrangement of the chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
structure via DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
or histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
modification may play a role as well. Here is a list of in vitro examples and in vivo examples. In vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
methods of transfecting specific mouse cells utilize the same kinds of vectors as in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
experiments, except that the vector is injected into a specific organ. Zhou et al. (2008) injected Ngn3, Pdx1 and Mafa into the dorsal splenic lobe (pancreas) of mice to reprogram pancreatic exocrine
Exocrine glands are glands that secrete substances on to an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of t ...
cells into β-cells in order to ameliorate hyperglycaemia.
Initial epigenetic activation phase approach
Somatic cells are first transfected with pluripotent reprogramming factors temporarily (Oct4
Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 (POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. I ...
, Sox2, Nanog, etc.) before being transfected with the desired inhibitory or activating factors. Here is a list of examples in vitro.
Pharmacological agents
The DNA methylation inhibitor, 5-azacytidine is also known to promote phenotypic transdifferentiation of cardiac cells to skeletal myoblasts.
In prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
, treatment with androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
targeted therapies induces neuroendocrine transdifferentiation in a subset of patients. No standard of care exists for these patients, and those diagnosed with treatment induced neuroendocrine carcinoma are typically treated palliatively.
Mechanism of action
The transcription factors serve as a short term trigger to an irreversible process. The transdifferentiation liver cells observed 8 months after one single injection of pdx1.
The ectopic transcription factors turn off the host repertoire of gene expression in each of the cells. However, the alternate desired repertoire is being turned on only in a subpopulation of predisposed cells. Despite the massive dedifferentiation – lineage tracing approach indeed demonstrates that transdifferentiation originates in adult cells.
Mogrify algorithm
Determining the unique set of cellular factors that is needed to be manipulated for each cell conversion is a long and costly process that involved much trial and error. As a result, this first step of identifying the key set of cellular factors for cell conversion is the major obstacle researchers face in the field of cell reprogramming. An international team of researchers have developed an algorithm, called Mogrify(1), that can predict the optimal set of cellular factors required to convert one human cell type to another. When tested, Mogrify was able to accurately predict the set of cellular factors required for previously published cell conversions correctly. To further validate Mogrify's predictive ability, the team conducted two novel cell conversions in the laboratory using human cells, and these were successful in both attempts solely using the predictions of Mogrify. Mogrify has been made available online for other researchers and scientists.
Issues
Evaluation
When examining transdifferentiated cells, it is important to look for markers of the target cell type and the absence of donor cell markers which can be accomplished using green fluorescent protein or immunodetection. It is also important to examine the cell function, epigenome
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome ...
, transcriptome
The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...
, and proteome
The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
profiles. Cells can also be evaluated based upon their ability to integrate into the corresponding tissue in vivo and functionally replace its natural counterpart. In one study, transdifferentiating tail-tip fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
into hepatocyte-like cells using transcription factors Gata4
Transcription factor GATA-4 is a protein that in humans is encoded by the ''GATA4'' gene.
Function
This gene encodes a member of the GATA family of zinc finger transcription factors. Members of this family recognize the GATA motif which is pr ...
, Hnf1α and Foxa3
Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) is a protein that in humans is encoded by the ''FOXA3'' gene.
Function
HNF-3G is a member of the forkhead class of DN ...
, and inactivation of p19(Arf) restored hepatocyte-like liver functions in only half of the mice using survival as a means of evaluation.
Transition from mouse to human cells
Generally transdifferentiation that occurs in mouse cells does not translate in effectiveness or speediness in human cells. Pang et al. found that while transcription factors Ascl1
Achaete-scute homolog 1 is a protein that in humans is encoded by the ''ASCL1'' gene. Because it was discovered subsequent to studies on its homolog in Drosophila, the Achaete-scute complex, it was originally named MASH-1 for mammalian achaete scu ...
, Brn2 and Myt1l turned mouse cells into mature neurons, the same set of factors only turned human cells into immature neurons. However, the addition of NeuroD1
Neurogenic differentiation 1 (Neurod1), also called β2, is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1.
In mice, ''Neurod1'' expression is first seen at embryonic day 12 (E12).
It is a member of the Neurod ...
was able to increase efficiency and help cells reach maturity.
Order of transcription factor expression
The order of expression of transcription factors can direct the fate of the cell. Iwasaki et al. (2006) showed that in hematopoietic lineages, the expression timing of Gata-2 and (C/EBPalpha) can change whether or not a lymphoid-committed progenitors can differentiate into granulocyte
Granulocytes are
cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...
/monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
progenitor, eosinophil
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
, basophil
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
or bipotent basophil
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
/mast cell
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
progenitor lineages.
Immunogenicity
It has been found for induced pluripotent stem cells that when injected into mice, the immune system of the synergeic mouse rejected the teratomas
A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx.
Symptoms
Symptoms may be minimal if the tumor is small. A testicular ter ...
forming. Part of this may be because the immune system recognized epigenetic markers of specific sequences of the injected cells. However, when embryonic stem cells were injected, the immune response was much lower. Whether or not this will occur within transdifferentiated cells remains to be researched.
Method of transfection
In order to accomplish transfection
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to desc ...
, one may use integrating viral vector
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...
s such as lentivirus
''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lent ...
es or retrovirus
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...
es, non-integrating vectors such as Sendai virus
''Murine respirovirus'', formerly ''Sendai virus'' (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped,150-200 nm in diameter, a negative sense, single-stranded RN ...
es or adenoviruses
Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
, microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s and a variety of other methods including using proteins and plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s; one example is the non-viral delivery of transcription factor-encoding plasmids with a polymeric carrier to elicit neuronal transdifferentiation of fibroblasts. When foreign molecules enter cells, one must take into account the possible drawbacks and potential to cause tumorous growth. Integrating viral vectors have the chance to cause mutations when inserted into the genome. One method of going around this is to excise the viral vector once reprogramming has occurred, an example being Cre-Lox recombination
Cre-Lox recombination is a site-specific recombinase technology, used to carry out deletions, insertions, translocations and inversions at specific sites in the DNA of cells. It allows the DNA modification to be targeted to a specific cell type ...
Non-integrating vectors have other issues concerning efficiency of reprogramming and also the removal of the vector. Other methods are relatively new fields and much remains to be discovered.
Pluripotent reprogramming
*Almost all factors that reprogram cells into pluripotency have been discovered and can turn a wide variety of cells back into induced pluripotent stem cells (iPSCs). However, many of the reprogramming factors that can change a cell's lineage have not been discovered and these factors apply only for that specific lineage.
*The final products of transdifferentiated cells are capable of being used for clinical studies, but iPSCs must be differentiated.
*It may become possible in the future to use transdifferentiation in vivo, whereas pluripotent reprogramming may cause teratomas in vivo.
*Transdifferentiated cells will require less epigenetic marks to be reset, whereas pluripotent reprogramming requires nearly all to be removed, which may become an issue during redifferentiation.
*Transdifferentiation is geared towards moving between similar lineages, whereas pluripotent reprogramming has unlimited potential.
*Pluripotent cells are capable of self-renewal and often go through many cell passages, which increases the chance of accumulating mutations. Cell culture may also favor cells that are adapted for surviving under those conditions, as opposed to inside an organism. Transdifferentiation requires fewer cell passages and would reduce the chance of mutations.
*Transdifferentiation can also be much more efficient than pluripotency reprogramming due to the extra step involved in the latter process.
*Both pluripotent and transdifferentiated cells use adult cells, thus starting cells are very accessible, whereas human embryonic stem cells require that one navigate legal loopholes and delve into the morality of stem cell research debate.
See also
* Epigenetics
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
* Induced pluripotent stem cell
Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...
* Induced stem cells
Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent – iM ...
* Reprogramming
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
...
References
*
{{Authority control
Biological processes
Induced stem cells