Hello!

I’ve been looking at induced pleuripotent stem cells and what forms of human tissues they can generate. IT seems as though many tissues and even a couple partial organs have already been generated. There is ALOT of literature on this! hahaha.

“To what degree are the inductive elements that are necessary for liver bud formation in the embryo the same as the inductive elements that are necessary for liver bud formation from induced pleuripotent stem cells (in rats or mice)?”

I have been thinking of different variations of this question with different organ/tissue systems or with different more specific parameters for inductive elements (such as a smaller list of specific known proteins).

Have a good day!

1. In class today we discussed the big ideas that drive limb formation, the development of an arm or a leg in humans. Malformation of the limb can be an extremely detrimental condition to live with and a better understanding of the processes behind limb formation could eventually yield results that will help medical practitioners to prevent or treat malformed limbs in an optimal way. Many conditions that affect proper limb growth affect many other things, this is because the components that are necessary for limb formation are used in many other areas of development (for example, dwarfism doesn’t only reduce the height of someone, it has many other negative symptoms, such as apnea or hydrocephalus that must be addressed to stay as healthy as possible). For the proper growth of limbs, an extremely specific set of machines in our body must coordinate together almost perfectly. Our DNA, a long double helix chain with instructions along it, must be bound by these machines in the proper way at the proper time by the proper elements to yield the products that DNA encodes (which is often MORE machinery!). This dance requires that all the other machines do what they need to, whether that be to help the proper machine bind to the DNA at the right time or to remove it when its job is done. This binding and unbinding is the major means by which our cells accomplish their goals, such as dividing precisely millions of times to yield dextrous functional digits. These pieces of cellular machinery have simple functions, but there are so many different variations and flavours of them that when they are exposed to slightly different conditions they can yield dramatically different results that culminate into cellular activity; their orchestration and interactions between one another is the key to understand how something like fingers to play piano or write a paragraph for class can come from a lump of seemingly insignificant and underwhelming cells.

The hardest part was avoiding jargon by far. To find the proper words to express your point without jumping into science-language is its own test.

The ZPA regulatory sequence (ZRS) controls SHH expression for the developing limb and is an enhancer. Transplantation experiments yielded results that showed altered digit expression, and the same was detected with mice that had increased SHH expression beyond the normal ZPA. a second ZPA was even detected more anterior presumably in part due to the differential expression of SHH. The ZRS region has been shown to be influenced by point mutations as well. The 2.2 kilobase region it covers likely interacts with the promoter region or another regulatory site to increase expression.

One could test this experimentally by taking identical specimens and altering only that 2.2 kilobase region and measuring the SHH levels at and around the ZPA against each specimen. A correlational study could be to test the SHH expression in individuals with limb disorders and individuals without limb disorders at and around the ZPA and then compare the degree of malformation to the degree of differences in SHH expression in the tested areas. The observational / discovery-based science approach could be to comb through genetic data and see which regions of DNA seem to be correlated with limb malformation, and hope to see the ZRS region.

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i. What are the factors or any potential signaling compounds that initiate spontaneous abortion or apoptosis in embryos at any given stage?

ii. What genetic modifications are necessary to transform/induce a wholly differentiated cell into a pleuripotent cell and by what mechanisms?

iii. What is the genetic/biochemical basis for humans’s heightened alcohol tolerance versus our recent common ancestors?

For ii:

I am interested in this broad question because even some small fraction of the answers to it could yield a source of stem cells that could be easily derived from almost any source. The potential of stem cells and their potential induction patterns has always made me dream of creative scientific/medical solutions to previously unsolved issues. I am excited to be alive during this time of exponential scientific data acquisition where creativity and knowledge can be so readily united in problem solving, and stem cells are one example of a relatively recent discovery that I can’t help but feel is going to explode in the next couple decades.

(And, frankly, I wish I knew more about stem cells than I do now!)

I realize this research is current and there have already been breakthroughs with some types of cells, like adipose, but further research could yield other types of convenient sources or more efficiently yielding and quicker processing techniques. The impact that would be had on the discipline of developmental genetics/biology would not change the whole field, but it would heavily influence it. An accurate description of all the mechanisms by which pleuripotency could be induced would yield much information that could be attributed throughout the many areas of developmental studies: The biochemical signal transduction  pathways would contribute  to the total sum knowledge and explain previously unknown results when dealing with the relevant compounds, the different stages of induction and the degree of specificity and determination could be rationalized/explained in a clear step-by-step mechanistic ways without needing whole tissue transplants to be performed, and there would be a higher availability of stem cells for all follow-up experimentation. Of all scientific fields, the largest impact would be upon medicine, whereby the availability of stem cells and their understanding would be greater. This means that therapeutic applications could be developed and applied to patients for cheaper. More advanced applications could also be developed than before and the efficiency of treatment would be increased. The community at large could benefit from these advancements if the knowledge is properly spread and it is made accessible to the general population around the world. Consistent full organ replacement, increased medical research potential, non-controversial stem cell sources, and economic efficiency for patient treatment are just some offhand examples of the benefits the public could benefit from.

-Reid Thomson