Cellular Time Travel: iPS Cells

Written By Vaishnavi Kolluru

Before I begin, I just wanna say it's nearing midnight and I'm not a night person (I'm not a morning person either lol but whatever) so I'm kinda cutting corners in this article. PLEASE dm me / leave a comment if you find anything cool in the linked papers, because I think this topic is super cool! I just don't have the brain capacity to read everything right now😭. That said, enjoy :)

Topic idea creds: @Allusion

Cellular potency describes the range of differentiation capability for a given stem cell. In other words, the potency describes which cell types the cell can eventually become. Types of potency include: totipotent, pluripotent, and multipotent. Totipotent cells can differentiate into both the embryo proper and the extraembryonic tissues (like the placenta). Pluripotent cells can differentiate into all cells of the embryo proper. They're called embryonic stem (ES) cells, as they can become any cells of the embryo. Multipotent cells can become any cells in a restricted range (ex: hematopoietic stem cells can become any kind of blood cell/platelet, but they can't become lung cells.)

This isn't really related to the matter of this article, so it's bad practice to put it in as a figure. I like it though; it's helpful and worth memorizing.

In 2006, something awesome happened: I was born. Additionally, Shinya Yamanaka and Kazutoshi Takahashi published the revolutionary, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors." I've linked the paper below, if you wanna read it. This was the world's first exposure to induced pluripotent cells (iPSCs). They essentially rewinded the cellular clock, making pretty well-differentiated mouse embryonic fibroblasts behave like pluripotent cells again. Their method consisted of introducing the c-Myc, Oct3/4, Sox2 and Klf4 genes (Yamanaka factors), which were previously identified (by other scientists) as pluripotency-maintaining factors, into cells. 

Ooh pretty!!!!!

These 4 genes encode transcription factors that induce pluripotency. These factors form the basis of the pluripotency gene regulatory network (PGRN). One important characteristic of the PGRN is that it exhibits bi-stability. This means that it has two equilibrium states; due to the interactions and downstream effects of the 4 core genes, either the pluripotent state is propagated among cells of the lineage (equilibrium position #1), or the 4 genes are downregulated by one another and themselves, and cellular differentiation ensues (equilibrium position #2). Note that the absence of pluripotency-inducing factors allows for differentiation. This is why addition of Yamanaka factors induced pluripotency. Consider the converse: suppose that the presence of differentiation-inducing factors is truly what allows differentiation, and their absence allows pluripotency. We would then have to remove/downregulate these factors to achieve pluripotency. Thankfully, this isn't the case, and we can add genes, which makes things WAY easier (but still not easy lolol).

Because iPSCs can be derived from embryonic cells (which destroys the embryo), many argue that iPSCs are unethical. Even when iPSCs are derived from somatic cells, the potential carcinogenicity (due to faulty rewinding of the cellular clock) adds to the ethical concerns of using iPSCs. I've linked an article below to learn more about the ethical debate.

Anyways, here are some more resources to learn about iPSCs:

Vaishnavi Kolluru
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