October 23, 2020

The Niche

Knoepfler lab stem cell blog

What are the best iPS cell papers so far?

What are the most important iPS cell papers so far?

1) Yamanaka’s first paper on mouse iPS cells. Revolutionary. Intriguing perspectives presented in day 1 of the iPS cell field. Interesting statements such as Myc is required. Also take a look at those other reprogramming factors that he tested…there’s a tremendous amount there, largely unexamined. This paper is an order of magnitude more important than any other in the iPS cell area. Read it carefully. Think.IPS cells, reprogramming

2) Hal Weintraub’s first paper reporting the existence of MyoD and the fact that its introduction could change fibroblasts into myoblasts that differentiate into myotubes. Weintraub’s was the first paper indicating that introducing a factor into cells could change their identity. Doesn’t that sound familiar to cellular reprogramming? Yes, in fact it was the FIRST cellular reprogramming. Yamanaka was a 26 year old medical resident when this paper was published. Read this paper carefully! Also, required reading includes these Weintraub lab papers from 1987 and 1988 (this latter one by one of my favorite scientists, Stephen Tapscott also of the Hutch) figuring out MyoD’s identity. I think Yamanaka should have cited Weintraub’s work in his first iPS cell paper. It should be also required reading for any review article on iPS cells in fact.

3) Wilmut’s cloning paper demonstrating that there are cytoplasmic factors that can reprogram the mammalian egg to pluripotency/totipotency yielding viable offspring. I’m thinking this paper (as well as others of course) stimulated Yamanaka and others to try to figure out what the factors are and come up with elegant schemes to identify them. This paper does not have iPS cell in the title or any iPS cell surrogate term, but I think it was a crucial paper. Hello, Dolly!

4) Yamanaka’s paper on human iPS cells.  Not as paradigm-shifting as his first on the mouse, but still very important. Some things that work in mouse cells do not work in human.

5) Thomson’s paper on human iPS cells. Interesting. Some different factors, but Oct4 still is king.

6) Daley’s iPS cell memory paper. iPS cells have epigenetic memories of their parental cells of origin. The parental cells do matter. iPS cells are not perfect.

7) Wernig’s first transdifferentiation paper. Wait, you might say, that’s not iPS cells! But actually it is all within the same grand domain. I believe Wernig was inspired by Yamanaka to pursue transdifferentiation.

8 ) Ding’s paper on getting small molecules into the iPS cell mix. This paper is important because it really paved the way for using small molecules in reprogramming and because it indicated that epigenetics was a key target. Another nice paper from the Ding lab added to the story and this Melton lab paper was also an early one on small molecules.

9 ) The “you don’t need Myc” Yamanaka paper. I believe this to be a very important paper for a number of reasons beyond the fact that I study Myc. First, it showed that contrary to what was originally thought that exogenous Myc is not formally required even if Myc increases efficiency 100-fold. It also raised the idea that maybe you could make clinically usable iPS cells. However, this paper is also important because of how it makes people think Myc was the only cancer-related obstacle, when in fact all the key pluripotency factors are linked in one way or another to cancer. There is also the issue of endogenous Myc.

10) Austin Smith’s 1998 Cell paper on Oct4. This was a seminal paper on the importance of Oct4. No, much like #2, it also does not have iPS cell or anything of that kind in the title. Why am I including it? It’s hard to imagine iPS cells existing without it. No data on Oct4 function in embryos means no knowledge of the importance of Oct4 in the ICM or ES cells and in turn no iPS cells. As revolutionary as Yamanaka’s iPS cells were, they were built based on the ES cell knowledge base. That work was done by the ES cell and early embryogenesis scientific community. We can’t forget that.

Why did I choose these 10 papers from the now cumulative total of almost 1,500 iPS cell papers*?

I think these papers first of all made iPS cells possible and of those specifically on iPS cells they are the highest impact so far. The list could change!
In my recent piece on taboo topics in the iPS cell field, I noted that one such topic was the reality that most papers published on iPS cells aren’t important. Some of these papers that I find rather forgettable nonetheless have hundreds of citations and a subset were published in top notch journals.

Why?

There could be any number of reasons.

They rode a short-lived, micro-trend that was hot in iPS cells, but isn’t any more. Perhaps they had a famous senior author? Failure of peer review?

If one goes simply by # of citations amongst the 1500, the list of the top 10 is below. You’ll see by comparing to my list above that I do not agree with the list based just on citation #’s.

ips cell papers

Do you have top 10 favorites not on my list? Let us know in the comments and tell us why!

*Title=(iPS cell OR iPS cells OR induced pluripotent stem cell OR induced pluripotent stem cells OR induced pluripotency OR induction pluripotent)

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