Neoblast

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Neoblast
Neoblastos.jpg
Distribution of Neoblasts throughout the body of a Schmidtea mediterranea planaria. Neoblasts appear throughout the body except for the pharynx shown by an arrow. Green dots are Neoblasts that are dividing, while red dots are Neoblasts that are not dividing.
Details
Gives rise to Blastema
Anatomical terminology

Neoblasts (ˈniːəʊˌblæst) are non-differentiated cells found in flatworms called planarians. Neoblasts make up about 30 percent of all cells in planaria. Neoblasts give planarians an extraordinary ability to regenerate lost body parts. A planarian split lengthwise or crosswise will regenerate into two separate individuals.

Contents

Characteristics

A neoblast is a non-differentiated cell found in planarians and are responsible for regeneration. Neoblasts have little cytoplasm and a huge nucleus which is a characteristic of pluripotent cells. They are the only dividing and growing cells in planaria. [1] This mitotic characteristic is how they are detected by adding Bromodeoxyuridine (BrdU) and staining with anti-BrdU. [1] They have a size between 5 µm to 8 µm in diameter. [2] Neoblasts represent about 30 percent of all cells in planaria. [3] They are not present in the anterior, posterior or pharynx. [1]

Neoblast form blastema capable of growth and regeneration into organs or body parts. Blastemas, in general, are typically found in the early stages of an organism's development such as in embryos, and in the regeneration of tissues, organs and bone. [4] [5]

Blastema formation

Neoblast specification during regeneration. Mechanism of neoblast specification during regeneration.jpg
Neoblast specification during regeneration.

In flatworms, the formation of a blastema needs adult stem cells that are called neoblasts for regeneration to occur. [6]

Right after amputation, a wound response is initiated. All cells in the wound area produce the same transcriptional response regardless of where the wound happened. [5] After this initial wound response, the transcriptional profile changes depending on the location. [5]

A regeneration blastema forms from clonogenic neoblasts (cNeoblast), which work as stem cells to replace older adult cells. [5]

Clonogenic neoblasts also move to a wound site and regenerate the tissue by producing dividing progenitor cells, and finally, all the specific cells. [5]

Transplantation of just one clonogenic neoblast, a worm with no neoblast, restored all the organism's cells. [5] One single neoblast can regenerate an entire irradiated animal that has been rendered incapable of regeneration following transplantation into an irradiated, neoblast-free worm, and this shows that at least some neoblasts are pluripotent. [7]

Some amount of endoderm is needed for blastema formation. [1]

Neoblast specialization

The gene smed-wi-1 is expressed by all neoblasts. [5]

There are two distinct populations of neoblasts, called zeta and sigma. [5] Zeta and sigma neoblasts look the same, but they have different gene regulatory networks. Also, zeta neoblasts are postmitotic, while sigma neoblasts are mitotic and specifically responsible for injury repair. Sigma neoblasts produce brain, intestine, muscle, excretory, pharynx, and eye cell types. They also lead to cells that become zeta neoblasts. Zeta neoblasts then develop the other epidermal cell types. [5]

Molecular characteristics

Components of chromatoid bodies

Neoblasts have chromatoid bodies, which are electronically dense structures composed of ribonucleoprotein complexes that are possibly responsible for maintaining neoblasts. Two protein components have been found within the chromatoid bodies DjCBC-1 and SpolTud-1, which are homologous to proteins involved in the proliferation of germline cells in other organisms. [8]

Piwi and the interaction of small RNAs in neoblasts

The Argonaut Piwi sub-family of proteins and the small RNAs that interact with them are essential for germline cell development, cell turnover, epigenetic regulation, and repression of transposable elements.  Planarians lacking or are deficient in the expression of piwi show defects in the maintenance and differentiation of cells of the germline. [9] A class of small non-coding RNAs are strongly expressed in neoblasts which serve as specific regulators for gene expression . These accompanied by the action of piwi would be the key regulators in the maintenance of the neoblasts. [10]

Involved Signaling Pathways

Several different signaling pathways are involved with limb regeneration through the formation of the blastema. After using RNA interference, Smad-beta-catenin-1 was found to set up the anterior-posterior axis. Inhibitions to this result in reversed polarity across the blastema. [6]

Transplantation of a single neoblast to a fatally injured animal has been shown to rescue the animal [11]

An analysis of the genome of S. mediterranea indicated the presence of a previously unknown family of long terminal repeats and the lack of several essential genes, including genes responsible for the synthesis of fatty acids and the MAD1 and MAD2 genes, which were thought to be essential components of the spindle assembly checkpoint. [12]

History

Regeneration research using planarians began in the late 1800s and was popularized by T.H. Morgan at the beginning of the 20th century. [13] Alejandro Sanchez-Alvarado and Philip Newmark transformed planarians into a model genetic organism in the beginning of the 20th century to study the molecular mechanisms underlying regeneration. [14] Morgan found that a piece corresponding to 1/279th of a planarian [13] or a fragment with as few as 10,000 cells could regenerate into a new worm within one to two weeks. [3] Morgan also found that if both the head and the tail were cut off a flatworm the middle segment would regenerate a head from the former anterior end and a tail from the former posterior end.

Schmidtea mediterranea has emerged as the species of choice for research due to its diploid chromosomes and the existence of both asexual and sexual strains. [15] Recent genetic screens utilizing double-stranded RNA technology have uncovered 240 genes that affect regeneration in S. mediterranea. Many of these genes have orthologs in the human genome. [16]

It used to be thought that old cells dedifferentiated and produced a regeneration blastema of undifferentiated cells to form the new structure using paracrine factors. [5] This was disproved in 2012. [5]

Application

The study of neoblasts helps uncover the mechanisms and functioning of stem cells and tissue degeneration. Planarians can regenerate any body part from small pieces in a few days and have many adult stem cells. They are easy to culture and grown to large populations. Their proteins are similar to human proteins. RNA interference is done by feeding, injecting, or soaking them in double-stranded RNA. The genome of Schmidtea mediterranea has been sequenced. In humans, no known pluripotent stem cells remain after birth. [17]

A collaborative research community on planarian research, EuroPlanNet, was launched in May 2010. [17]

Related Research Articles

Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of regeneration, asexual reproduction, metamorphosis, and the growth and differentiation of stem cells in the adult organism.

Whitehead Institute

Whitehead Institute for Biomedical Research is a non-profit research institute located in Cambridge, Massachusetts, United States that is dedicated to improving human health through basic biomedical research. It was founded as a fiscally independent entity from the Massachusetts Institute of Technology (MIT), where its 18 members all hold faculty appointments in the MIT Department of Biology or the MIT Department of Bioengineering. Two members are National Medal of Science recipients; ten have been elected to the National Academy of Sciences; and four have been elected to the National Academy of Medicine; six are Howard Hughes Medical Institute Investigators.

Planarian Flatworms of the Turbellaria class

A planarian is one of many flatworms of the traditional class Turbellaria. It usually describes free-living flatworms of the order Tricladida (triclads), although this common name is also used for a wide number of free-living platyhelminthes. Planaria are common to many parts of the world, living in both saltwater and freshwater ponds and rivers. Some species are terrestrial and are found under logs, in or on the soil, and on plants in humid areas.

Regeneration (biology) Biological process of renewal, restoration, and tissue growth

In biology, regeneration is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete where after the necrotic tissue comes fibrosis.

Oct-4

Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.

Morphallaxis is the regeneration of specific tissue in a variety of organisms due to loss or death of the existing tissue. The word comes from the Greek allazein, (αλλάζειν) which means to change.

Blastema Mass of cells capable of enacting growth and regeneration

A blastema is a mass of cells capable of growth and regeneration into organs or body parts. Historically, blastemas were thought to be composed of undifferentiated pluripotent cells, but recent research indicates that in some organisms blastemas may retain memory of tissue origin. Blastemas are typically found in the early stages of an organism's development such as in embryos, and in the regeneration of tissues, organs and bone.

Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposable elements and other spurious or repeat-derived transcripts, but can also be involved in the regulation of other genetic elements in germ line cells.

Piwi

Piwi genes were identified as regulatory proteins responsible for stem cell and germ cell differentiation. Piwi is an abbreviation of P-elementInduced WImpy testis in Drosophila. Piwi proteins are highly conserved RNA-binding proteins and are present in both plants and animals. Piwi proteins belong to the Argonaute/Piwi family and have been classified as nuclear proteins. Studies on Drosophila have also indicated that Piwi proteins have slicer activity conferred by the presence of the Piwi domain. In addition, Piwi associates with heterochromatin protein 1, an epigenetic modifier, and piRNA-complementary sequences. These are indications of the role Piwi plays in epigenetic regulation. Piwi proteins are also thought to control the biogenesis of piRNA as many Piwi-like proteins contain slicer activity which would allow Piwi proteins to process precursor piRNA into mature piRNA.

Induced pluripotent stem cell Pluripotent stem cell generated directly from a somatic cell

Induced pluripotent stem cells 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 2006 that the introduction of four specific genes, collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."

PIWIL1

Piwi-like protein 1 is a protein that in humans is encoded by the PIWIL1 gene.

Cell potency Ability of a cell to differentiate into other cell types

Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.

<i>Schmidtea mediterranea</i> Species of worm

Schmidtea mediterranea is a freshwater triclad that lives in southern Europe and Tunisia. It is a model for regeneration, stem cells and development of tissues such as the brain and germline.

Vasa is an RNA binding protein with an ATP-dependent RNA helicase that is a member of the DEAD box family of proteins. The vasa gene, is essential for germ cell development and was first identified in Drosophila melanogaster, but has since been found to be conserved in a variety of vertebrates and invertebrates including humans. The Vasa protein is found primarily in germ cells in embryos and adults, where it is involved in germ cell determination and function, as well as in multipotent stem cells, where its exact function is unknown.

<i>Schmidtea</i>

Schmidtea is a freshwater triclad genus widely used in regeneration and developmental studies.

Transposon silencing is a form of transcriptional gene silencing targeting transposons. Transcriptional gene silencing is a product of histone modifications that prevent the transcription of a particular area of DNA. Transcriptional silencing of transposons is crucial to the maintenance of a genome. The “jumping” of transposons generates genomic instability and can cause extremely deleterious mutations. Transposable element insertions have been linked to many diseases including hemophilia, severe combined immunodeficiency, and predisposition to cancer. The silencing of transposons is therefore extremely critical in the germline in order to stop transposon mutations from developing and being passed on to the next generation. Additionally, these epigenetic defenses against transposons can be heritable. Studies in Drosophila, Arabidopsis thaliana, and mice all indicate that small interfering RNAs are responsible for transposon silencing. In animals, these siRNAS and piRNAs are most active in the gonads.

Epimorphosis is defined as the regeneration of a specific part of an organism in a way that involves extensive cell proliferation of somatic stem cells, dedifferentiation, and reformation, as well as blastema formation. Epimorphosis can be considered a simple model for development, though it only occurs in tissues surrounding the site of injury rather than occurring system-wide. Epimorphosis restores the anatomy of the organism and the original polarity that existed before the destruction of the tissue and/or a structure of the organism. Epimorphosis regeneration can be observed in both vertebrates and invertebrates such as the common examples: salamanders, annelidas, and planarians.

Alejandro Sánchez Alvarado

Alejandro Sánchez Alvarado is a molecular biologist, an investigator of the Howard Hughes Medical Institute, and Executive Director and Chief Scientific Officer of the Stowers Institute for Medical Research. The Sánchez Alvarado Laboratory focuses on understanding the regenerative capabilities of the planarian flatworm Schmidtea mediterranea. In 2015, Sánchez Alvarado was elected a fellow of the American Academy of Arts and Sciences, and to the National Academy of Sciences in 2018 for his distinguished and continuing achievements in original scientific research.

Piwi like rna-mediated gene silencing 4

Piwi like RNA-mediated gene silencing 4 is a protein that in humans is encoded by the PIWIL4 gene.

Dedifferentiation is a transient process by which cells become less specialized and return to an earlier cell state within the same lineage. This suggests an increase in a cell potency, meaning that after dedifferentiation, cells may possess an ability to redifferentiate into more cell types than it did before. This is in contrast to differentiation, where differences in gene expression, morphology, or physiology arise in a cell, making its function increasingly specialized.

References

  1. 1 2 3 4 Reddien, Peter W.; Alvarado, Alejandro Sánchez (2004). "Fundamentals of Planarian Regeneration". Annual Review of Cell and Developmental Biology. 20: 725–757. doi:10.1146/annurev.cellbio.20.010403.095114. PMID   15473858.
  2. Reddien, P. W. (2013). "Specialized progenitors and regeneration". Development. 140 (5): 951–957. doi:10.1242/dev.080499. PMC   3583037 . PMID   23404104. S2CID   18178934.
  3. 1 2 Montgomery JR, Coward SJ (July 1974). "On the minimal size of a planarian capable of regeneration". Transactions of the American Microscopical Society. 93 (3): 386–91. doi:10.2307/3225439. JSTOR   3225439. PMID   4853459.
  4. Tanaka EM, Reddien PW (July 2011). "The cellular basis for animal regeneration". Dev. Cell. 21 (1): 172–85. doi:10.1016/j.devcel.2011.06.016. PMC   3139400 . PMID   21763617.
  5. 1 2 3 4 5 6 7 8 9 10 11 Barresi, Michael; Gilbert, Scott (July 2019). Developmental Biology (12th ed.). Oxford University Press. ISBN   978-1605358222.
  6. 1 2 Petersen CP, Reddien PW (January 2008). "Smed-betacatenin-1 is required for anteroposterior blastema polarity in planarian regeneration". Science. 319 (5861): 327–30. Bibcode:2008Sci...319..327P. doi:10.1126/science.1149943. PMID   18063755. S2CID   37675858.
  7. "Flatworms, the masters of regeneration – but nothing can happen without stem cells". Max Planck Institute for Molecular Biomedicine, Münster.
  8. Yoshida-Kashikawa, Maki; Shibata, Norito; Takechi, Katsuaki; Agata, Kiyokazu (2007). "DJCBC-1, a conserved DEAD box RNA helicase of the RCK/P54/Me31B family, is a component of RNA-protein complexes in planarian stem cells and neurons". Developmental Dynamics. 236 (12): 3436–3450. doi: 10.1002/dvdy.21375 . PMID   17994545. S2CID   35919013.
  9. Carmell, Michelle A.; Girard, Angélique; Van De Kant, Henk J.G.; Bourc'His, Deborah; Bestor, Timothy H.; De Rooij, Dirk G.; Hannon, Gregory J. (2007). "MIWI2 is Essential for Spermatogenesis and Repression of Transposons in the Mouse Male Germline". Developmental Cell. 12 (4): 503–514. doi: 10.1016/j.devcel.2007.03.001 . PMID   17395546.
  10. Palakodeti, D.; Smielewska, M.; Graveley, B. R. (2006). "MicroRNAs from the Planarian Schmidtea mediterranea: A model system for stem cell biology". RNA. 12 (9): 1640–1649. doi:10.1261/rna.117206. PMC   1557691 . PMID   16849698.
  11. Wagner, Daniel E.; Wang, Irving E.; Reddien, Peter W. (13 May 2011). "Clonogenic Neoblasts Are Pluripotent Adult Stem Cells That Underlie Planarian Regeneration". Science. 332 (6031): 811–816. Bibcode:2011Sci...332..811W. doi:10.1126/science.1203983. hdl:1721.1/110557. ISSN   0036-8075. PMC   3338249 . PMID   21566185.
  12. Grohme, M. A.; Schloissnig, S.; Rozanski, A.; Pippel, M.; Young, G. R.; Winkler, S.; Brandl, H.; Henry, I.; Dahl, A.; Powell, S.; Hiller, M.; Myers, E.; Rink, J. C. (2018). "The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms". Nature. 554 (7690): 56–61. Bibcode:2018Natur.554...56G. doi:10.1038/nature25473. PMC   5797480 . PMID   29364871.
  13. 1 2 Morgan TH (1900). "Regeneration in Planarians". Archiv für Entwicklungsmechanik der Organismen. 10 (1): 58–119. doi:10.1007/BF02156347. hdl: 2027/hvd.32044107333064 . S2CID   33712732.
  14. Sánchez Alvarado A, Newmark PA (1998). "The use of planarians to dissect the molecular basis of metazoan regeneration". Wound Repair and Regeneration. 6 (4): 413–20. doi:10.1046/j.1524-475x.1998.60418.x. PMID   9824561. S2CID   8085897.
  15. Newmark PA, Sánchez Alvarado A (March 2002). "Not your father's planarian: a classic model enters the era of functional genomics". Nature Reviews. Genetics. 3 (3): 210–9. doi:10.1038/nrg759. PMID   11972158. S2CID   28379017.
  16. Developmental Biology; Brandon castaneda Tec. "Regeneration in S. mediterranea" . Retrieved 31 March 2014.
  17. 1 2 Gentile, L.; Cebria, F.; Bartscherer, K. (2011). "The planarian flatworm: An in vivo model for stem cell biology and nervous system regeneration". Disease Models & Mechanisms. 4 (1): 12–19. doi:10.1242/dmm.006692. PMC   3014342 . PMID   21135057. S2CID   2478930.