#pluripotency

[cancer-researcher]

[thepurplelilac]

It’s #Oct4, so it's time to celebrate #PluripotencyDay! Here are some photos of my human embryonic #pluripotentcells stained with #pluripotency marker oct4 (green) #sciart #stemcells https://www.instagram.com/p/CjS935ruvNn/?igshid=NGJjMDIxMWI=

[brudnopis]

Researchers induce pluripotency in differentiated canine cells for the first time

Dogs have been faithful human companions ever since their domestication thousands of years ago. With improvements in veterinary medicine in recent decades, their life expectancy has increased. However, an unfortunate side effect of this longevity, much like in humans, has been an increase in the occurrence of chronic and degenerative conditions.

[whyitscool]

What is a stem cell?

You once consisted of a single cell, too small to see without a microscope. Your entire body is descended from that single cell: your blood cells, skin cells, liver cells, and neural cells, all cousins. That first cell had the ability to produce each of these cell types and more, but as that cell divided and multiplied into an embryo, each subsequent generation of cells grew more specialized and the number of roles it could eventually perform narrowed.

Cells that have the capacity to mature into multiple different cell types are called stem cells. The ones I described above are embryonic stem cells, but adults have stem cells in their bodies too. The most famous of these are the hematopoetic stem cells, which mature into different kinds of blood cells (white blood cells, red blood cells, platelets, and others.) Other active stem cells reside in your digestive tract and hair follicles. 

(This is essentially why some chemotherapies cause nausea and hair loss. Fighting cancer means preventing rapidly-dividing cells from growing into tumors, but it often impacts other rapidly-growing cell types as well.)

You may have noticed a major difference between these embryonic and adult stem cell types. While the first cells of an embryo go on to eventually form every cell in a human body, the adult stem cells are already relatively specialized. One kind of adult stem cell forms blood cells, another kind forms skin cells, and so on. 

This difference is pluripotency. A pluripotent stem cell has the ability to form every cell that makes up the human body. Adult stem cells, on the other hand, are multipotent: they can form many different types of cells, but not all.

(The first few cells of a zygote are actually totipotent: they can form not only all the cells in a human body, but also all the cells to make up a placenta.)

Pluripotent stem cells are of significant biological interest; scientific dreams of growing new organs and stalling neurodegenerative damage rely on their availability. But they have been the focus of significant ethical controversy. Pluripotent stem cells are naturally only found in embryos, and that's where they came from for early stem cell research.

Human embryonic stem cells are derived from embryos discarded by in vitro fertilization clinics, which often fertilize multiple eggs to increase their chances of success, but only advance pregnancy with one. No embryo has ever been created for stem cell research, and all embryos used for scientific research would have died regardless of their research use. Still, the ethical ramifications remain murky and controversial.

Enter induced pluripotent stem cells.

"In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically "reprogrammed" to assume a stem cell-like state.

Through research on embryonic stem cells (though often using nonhuman embryos), the scientists found genes responsible for making embryonic stem cells pluripotent. Since then, other research has been able to replicate this finding without the use certain genes that promote tumors.

(This is a constant challenge of working with stem cells. Cancer cells are no longer bound by normal rules about when to multiply, often because they have turned on genes from embryonic development that direct cells to grow and divide. Overlap between embryonic development and tumor development exists in the very definitions of those processes.)

Because of this research, it is now possible to take skin cell samples from an adult and create embryonic-like stem cells from them. 

It's important to note that an embryo cannot be created this way, so don't get too excited about the future of cloning - the cells aren't totipotent, meaning they cannot develop into a placenta, and thus cannot support embryo growth. However, by influencing their environments regulating their development, they can be induced to grow into a variety of different cell types.

Sidestepping the ethical dilemma of embryonic stem cells is a major advantage to induced pluripotency, but it isn't the only one. When stem cells are created from an adult patient, they are guaranteed to be a genetic and immunological match. Although directing such cells to develop into complex structures (i.e. growing new organs) remains unrealistic, it is possible to grow new cells to replenish failing populations, and the first disease treatments using induced pluripotent stem cells are beginning clinical trials.

It should be noted that as of 2016, no such treatments have cleared trials, so any clinic claiming to be using stem cell treatments is either making use of dangerously unregulated science or, more likely, lying. The only approved medical uses for stem cells are grafting stem cell tissue from a donor, as in a bone marrow transplant.

Current efforts using induced pluripotent stem cells are developing treatments for a variety of diseases: from macular degeneration, to regrow damaged rods and cones in the eye; to multiple sclerosis and other autoimmune disorders, to "reboot" immune systems; to Parkinson's disease, to introduce new dopamine-producing neurons to supplement failing ones.

Thanks to induced pluripotency, it is now possible to grow a petri dish full of neurons out of a skin sample. But if scientists have their way, that won’t be the coolest thing to come out of this technology by a long shot.

[larryhbernsteinme]

3D “Squeeze” Helps Adult Cells Become Stem Cells

3D “Squeeze” Helps Adult Cells Become Stem Cells

3D “Squeeze” Helps Adult Cells Become Stem Cells

Reported by: Irina Robu, PhD

Scientists based at Ecole Polytechnique Fédérale de Lausanne led by Matthias Lutolf have been engineering 3D extracellular matrices—gels. These scientists report that they have developed a gel that boosts the ability of normal cells to revert into stem cells by simply “squeezing” them.

The detail of the scientists’ work…

View On WordPress

[currentsinbiology]

From pluripotency to totipotency

While it is already possible to obtain in vitro pluripotent cells (ie, cells capable of generating all tissues of an embryo) from any cell type, researchers from Maria-Elena Torres-Padilla’s team have pushed the limits of science even further. They managed to obtain totipotent cells with the same characteristics as those of the earliest embryonic stages and with even more interesting properties. Obtained in collaboration with Juanma Vaquerizas from the Max Planck Institute for Molecular Biomedicine (Münster, Germany), these results are published on 3rd of August in the journal Nature Structural & Molecular Biology.

Human embryonic stem cells have the potential to form in vitro neural tube -like structures of the embryo. ©Inserm/Benchoua Alexandra

[scirp]

Read the full paper at: http://www.scirp.org/journal/PaperInformation.aspx?PaperID=49828 DOI: 10.4236/scd.2014.44012 Author(s) Vinod Verma, Ashish Mehta, Sanjay Pal, Manoj Kumar, Birbal Singh, Ashok Kumar, Sanjeev Gautam ABSTRACT Treatments to repair the human heart following regenerative diseases remain a challenge for medical science. Unlike lower vertebrate species the human heart lacks a regenerative pathway meaning that research has to be focused on cell transplantation. Porcines (Sus scrofa) are excellent models for cardiovascular disease and pluripotent stem cells (PSCs) generated from porcines will provide important clinical insights for cardiac cell therapy. EWW140923GJR This could open a new avenue of research into degenerative conditions as porcine is a more effective human proxy to work with. However, bona fide PSCs are currently available onlyin rodents (mouse, rat) and primates (monkey, human). Attempts to derivepluripotent stem cells (PSCs) from porcine have been going on for more than two decades with slow progress. Despite the fact that the porcine stem cells are under increasing glare of publicity due to milestone achievements in this area of research. Advances in stem cell technology, especially the genetic engineering, innovative cell culturing and induced pluripotency to generate stem cells has dramatically revolutionized the basic and applied investigations and applications of porcine stem cells. This review attempts to summarize the major signaling pathways involved in maintenance of pluripotency and the state of the art conceptual and technical progress for generating bona fide porcine PSCs. KEYWORDS Porcine Model, Signaling Pathways, Stem Cells, Induced Pluripotent Stem Cells, Pluripotency, Regenerative Medicine, Cell Therapy, Epigenetics

[phil-iannaccone]

SOX - really?

How can a fruit fly the size of the tip of a pencil (right) help a rhinoceros the size of a truck (left).  Hint: It's in the genes....read on.

June 17th, 2014

Last time we discussed how cloning led to the discovery nuclear reprogramming and a way to make stem cells from adult cells in a dish instead of from embryos. It is a method that generates cells for drug testing and new therapies in humans without the destruction of a human embryo. We saw that from a very large number of genes that are important in early development just four genes added to adult cells reset the biology of the cell so that it behaved as if it were part of an embryo and maintained the capacity to differentiate (turn into) virtually any type of cell in the body. These four genes are OCT4, SOX2, cMYC and KLF4. In some studies the gene NANOG was used instead of KLF4.

These genes were inserted into the cells at first using viruses, but later with other methods. The promise of essentially unlimited numbers of a cell type that can become heart cells, nerve cells, liver cells or whatever cells from any patient is incredibly important offering a way to replace damaged tissues, correct metabolic diseases like diabetes by replacing the diseased cells and many other applications.

But why these genes?

They were part of a large number of genes that regulate differentiation and cell division during embryonic development but there is not an adequate theory to explain why those particular genes are necessary and sufficient to make an adult cell behave as if it is an embryonic cell. Although the proteins that OCT4 and SOX2 code for stick to each other (bind) and together regulate (turn on) a large number of other genes that are known to prevent differentiation and therefore would maintain the potential of a cell to turn into many different types of specialized cells, a characteristic of stem cells. OCT4 (short for the name octamer-binding transcription factor 4; see how we name genes) is a master regulator of pluripotency, that is, the potential to differentiate into many types of cells. This is a critical attribute in cells of the early embryo. It is in a class of genes first discovered in the lowly (or mighty!) fruit fly. SOX2 (short for sex determining region box 2) is critical to self-renewal. This means that every time a stem cell divides at least 1 daughter cell is also a stem cell. This is why these cells can potentially supply an unlimited number of cells for research or therapy. cMYC (short for myelocytomatosis viral oncogene homologue; cytoplasmic) was discovered because it was mutated or broken in Burkitt lymphoma a cancer of blood cells. It regulates as many of 15% of all other genes (that’s like more than 4,000 genes)!! It is a key regulator of cell division and in addition to turning other genes on and off it also controls proteins that modify chromatin to allow other regulators access to genes.

Remember that genes are DNA embedded in chromatin that have many proteins and are organized in little regularly spaced balls. KLF4 (short for the name Krüppel like factor 4) is a member of a very large family of genes that all code for similar proteins. KLF4 is present in stem cells and can be used to identify cells as stem cells. NANOG, used by some scientists instead of KLF4 is reported to have been named after a Celtic myth about a land of everlasting youth. It is one of the key regulators of pluripotency and self-renewal. All of these genes are transcription factors, which means they attach themselves to the DNA of genes and switch the genes they are attached to on or off. Thereby they regulate the function of other genes. The fact that two of the four genes inserted into adult cells to make them into stem cells are oncogenes (or genes that cause cancer) gives great pause in the rush of enthusiasm surrounding using induced Pluripotent Stem Cells (iPSC) in human therapy. Further the viruses that are used to put these genes into cells change those cells in important other ways that can cause problems. And the viral genes remain in the cells. Finally we have already seen that stem cells injected into animals can cause teratomas and teratocarcinomas. The iPSC injected into animals developed into these teratomas. Alternative methods are being developed and studied to avoid these problems. By using RNA instead of genes the insertion and permanent expression of the four genes can be avoided. Apparently it is enough to activate the networks of genes that control stemmyness and the threat from cancer causing genes can be overcome. We will discuss more of the therapies that are being developed based on these cells soon but one fascinating application is underway in the forests of Borneo. Borneo and Malaysia are home to highly endangered species of Sumatran Rhinoceros, hunted to near extinction in the venal belief that powder from their horns increases sexual performance in men.  One of our scientists, Dr. Vasil Galat at the Research Institute is part of a team that the governments of Malaysia and Borneo assembled to produce iPSC from individual rhinoceri. These stem cells will be used in a variety of ways, including producing chimeric embryos with closely related species, but also have the potential to be developed into sperm cells and oocytes that can be used in IVF to increase the number of these wonderful creatures. Wow! From the teeny tiny fruit fly to the enormous rhinoceros!