Am I allowed to mention physics here? How about if it’s a rap video?
Pharyngula
Evolution, development, and random biological ejaculations from a godless liberal
Am I allowed to mention physics here? How about if it’s a rap video?
Wow…so have you heard about this result?
One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble β-cells. The induced β-cells are indistinguishable from endogenous islet β-cells in size, shape and ultrastructure. They express genes essential for β-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
This is a big deal, I think, so allow me to translate.
First, a little caveat: this is a recent result published in Nature, and it is basic science, not clinical work. Before you start thinking it’s a new treatment for diabetes, I have to dash a little cold water on you and warn you that this has a long, long way to go before it can be applied to humans…but it does open the door to some future strategies that might be applied.
The pancreas is a fairly complicated organ. It’s made up of a variety of different cells that we can toss into a couple of different classes. There are garden variety support cells — mesenchyme, connective tissue, components of the circulatory system, and the ductwork of the organ — that provide building services for the other cell types. Then there are exocrine cells, cells that produce quantities of important substances that are piped directly into the digestive tract via ducts. Among the most important materials exported by this route are bicarbonate buffers to neutralize stomach acids and enzymes like amylase to digest sugars. Finally, the class of cells that most people are familiar with, because they are the subject of a common disease, are the endocrine cells. These are cells that generate hormonal signals that are secreted into the blood stream, and the most familiar of these are the beta (β) cells, which are organized into clumps called islets and which secrete insulin…and if something goes awry with the β cells, the resulting disease is called diabetes.
What the researchers did was identify a small subset of transcription factors, the genes Ngn3, Pdx1 and Mafa, that are sufficient to switch on the insulin production genes in non-insulin-producing cells of the pancreas. They can turn exocrine cells into β cells, which produce insulin, and these cells reduce the effects of diabetes.
The way they did this was to insert the transcription factors (and a gene that makes a glowing protein, GFP, as a marker) into adenoviruses, and then inject the virus directly into the pancreases of genetically immunodeficient (to reduce immune response complications) adult mice. The viruses infected a subset of the pancreatic cells, preferentially the exocrine cells, and started pumping out the transcription factors. As is common in these kinds of genetic engineering experiments, the use of viral transfection is perhaps the scariest part of the story; viruses aren’t trivial to keep in check. However, they report that they also did later PCR tests of adjacent tissues and found no evidence that the virus spread beyond the target organ; they also found that inducing the expression of the 3 transcription factors in other kinds of cells, like muscle, seems to do nothing. These genes are only potent in pancreatic cells that are already primed to be competent to respond to the signals generated by the transcription factors.
The virus is also not needed for long term maintenance of these cells. The virus in the pancreas, as determined by PCR, is cleared away after about 2 months. It seems that all it takes is a brief jolt of expression of Ngn3, Pdx1 and Mafa to switch susceptible cells into the β cell state, and that the developmental program is then self-sustaining.
The authors also made diabetic mice by injecting them with streptozotocin, which kills islet β cells, and then gave them the viral cocktail injection. It did not cure their diabetes, but it did give them significantly greater glucose tolerance, and they did measure increased blood insulin levels. One reason the treatment may not be as effective as it could be is that it simply converts random, scattered exocrine cells into single β cells that are not organized into the islets of the normal pancreas.
A lot of attention has been paid to embryonic stem cell and adult stem cell technologies, and those are both important and provide research and treatment opportunities that must not be neglected, but this is a third way: mastering the developmental control genes of the cell so that we can reprogram mature cells into any cell type we need. While injecting a person’s pancreas with a collection of viruses to rebuild missing cell types might be a little hazardous and crude, there may come a day when we can collect a few cells from an individual by a scraping or biopsy, grow them in a dish to get enough, tickle their transcription factors to cause them to differentiate into the cell, tissue, or organ type we want, and transplant the final, immunocompatible product right back into the patient.
This is the direction developmental medicine can take us — I hope you’re all ready to support it.
Zhou Q, Brown J, Kanarek A, Rajagopa J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature Aug 27. [Epub ahead of print].
Here follows a brief account of my sojourn in the Galápagos Islands, just to give you all a rough idea of what I was up to all this time. I’ve tossed in just a few pictures to illustrate what we experienced; I’m planning to dole out the rest a little bit at a time, each week. I took a lot of pictures, and I was a real piker compared to a few other people on the trip — I’m thinking that if I use mine and some of the other photographs people took, if I post one a week, I’ll be able to keep the blog going for about 3800 years.
Since it has been a long time since I contributed any content to Pharyngula…here’s something. I was asked to give a brief talk on the ship, so I’ve tossed my written draft below the fold. With these short talks I like to write the story first, but when I get up on the stage and actually perform it, I don’t bring notes or anything like that, so what is actually said follows the structure of what I wrote, and some of the wording comes through, but it tends to be rather different. Probably a lot different —I know I extemporized a fair bit on the last half. This is all you get until I’ve had a good night’s sleep, though.
Some more pure science from guest blogger LisaJ:
Everyone seems to love a little Sonic Hedgehog around here. Whenever PZ discusses another function that this fascinating gene is capable of, much excitement ensues in the comment posts. So I thought I would take this opportunity to talk a bit about what I study, and how my seemingly unrelated favourite protein pathway is also connected to the Shh gene.
The main protein that I study was originally identified through studies of a pediatric eye cancer, called Retinoblastoma, as loss of function of this protein (termed the Retinoblastoma protein, or pRb for short) was found to be causative in the formation of this tumour type. What we know now is that pRb is required to control normal cell division in all cell types; its functional loss leads to the formation of many types of tumours, and is thought to be involved in the development of at least half of all human cancers. Not only is pRb essential in preventing uncontrolled cell division that can lead to cancer, but it is also essential for embryonic development, as mice deficient for the Rb gene die by about the 15th day of gestation, about 5 days before they would be born.
To explain how pRb functions in the cell, I thought that I could easily pull out a figure from a review paper that diagrams a simplified cell cycle pathway and the protein interactions that take place. But instead, I’m going to show you this beautiful piece of work that a few of my talented previous lab mates created for me one day, as a means of cheering me up after a year’s worth of protein purifications and binding assays did not give me the result I was hoping for. Although a simplistic depiction of cell cycle regulation, I think it really drives home the point well of how pRb functions.
Imagine you’re a paleontologist, digging through the Sahara desert looking for dinosaur bones and you stumble, instead, upon this wondrous find:
That’s exactly what happened to Paleontologist Paul Sereno and his team back in 2000, and they have announced their findings from their excavations of this region in Northern Niger in National Geographic this week. This team unexpectedly unearthed 200 human burials on the shores of a long dried up lake, representing two very distinct cultures spanning 5000 years (between 4500 to about 9000 years ago). The image shown above is of their ‘most striking discovery’, and depicts a woman and two children, ages 5 and 8, holding hands. They also found pollen in the grave, suggesting that they may have been laid on a bed of flowers. Very cool stuff. These researchers have located the remnants of two human tribes that are thought to have lived in the Sahara during the Holocene period, when environmental factors culminated in a ‘greening’ of the desert, which attracted human inhabitants.
Here’s a video featuring an interview with Paul Sereno and some nice shots of their excavation sites. They give a really nice overview of what they have discovered about the two distinct colonies found, and how they may have lived. You can also read the whole story in National Geographic, if you’re so inclined, where you will also find a link to additional photos of the site and their excavations, which are quite amazing.
Here’s a link to the study’s paper appearing in the current issue of PLoS ONE.
From guest blogger LisaJ
Here’s an awesome video of the most recent solar eclipse that took place a couple of weeks ago. This group was lucky enough to witness the eclipse from their airplane seats! You can see the eclipse pretty much from start to finish. Wait it out until the end, because it’s an amazing view when the sun comes back out. (Posted by LisaJ).
Here’s the open thread for comments about the Evolve episode on the History Channel-or anything else you’d like to chat about.
And here’s a classic post by PZ on the subject of vertebrate jaw evolution, just to get you warmed up. Enjoy!
~Danio
PZ has been live-blogging the new “Evolve” series on the History Channel since it began a few weeks ago. This week’s episode is on the evolution of jaws, and should be a good one. Alas, none of the Minions will be able to live-blog the program, but I will post an ‘Evolve’ open thread in time for the East Coast airing at 10 PM Tuesday night, in case anyone is interested in commenting as they watch.
Danio, for the collective.
Posted by LisaJ
Now this is a super cool new Science story. Have you ever wanted to make yourself invisible? Ever said “man, I wish I could just run away or hide and make everyone go away”? Maybe as a young 8 year old, trying to hide from those bullies on the playground. Or perhaps you’d like to saunter into mass inconspicuously one Sunday morning to grab one of those delicious wafers without starting a riot. Well, if this sounds like you, then your lucky day is (almost) here. Dr. Xiang Zhang and his group from the University of California have reportedly “created a material that could render people and objects invisible”. They are announcing this week, in a pair of articles to be published in Nature and Science, their generation of a 3D metamaterial that exhibits a negative refractive index (thanks negentropyeater). ‘Metamaterials’ are apparently a manmade mixture of metal and ceramic or Teflon like materials (anyone who knows anything about this field is welcome to clarify this!) that function to bend visible light waves quite aptly. These researchers have harnessed this unusual property of the metamaterial they have created to redirect light around 3D objects to effectively disguise or ‘cloak’ them.
This new study represents a major progression in the field, as previously this technology could only be used to cloak very thin 2D objects. Now I’m assuming that the 3D objects they effectively made invisible in these studies were probably pretty small too, we’ll have to wait until the end of the week to find out, but this is a big step closer to allowing humans to obtain their own invisibility cloaks.
This article explains that this ‘new work moves scientists a step closer to hiding people and objects from visible light, which could have broad applications, including military ones. ‘ Which is a pretty cool application, I guess (but also a very frightening one when you think about it). I think it’s pretty obvious what the greatest potential of this new technology really is: to make millions of Harry Potter fans very, very happy. You make a real invisibility cloak and you’ve hit a goldmine with that fanbase.
Now I am by no means a mechanical engineer, materials scientist, or an expert in this particular field. So if anyone would like to add any additional info on how this technology works it would be much appreciated. It sounds very cool, and I’d like to learn more.
