New Genomic Study of Placenta Finds Deep Links to Cancer

[Mercer (John Mercer)]

@John_Harshman

I don’t understand that explanation. Are you suggesting that the sample is biased because aneuploid embryos don’t make it to the stage at which they can be sampled?

No.

@John_Harshman

What we have here is, apparently, aneuploid fetal cells in the placenta but normal fetal cells in the embryo. How does selection account for that?

Selection would be stronger in the embryo than in the placenta.

[thoughtful (Valerie (non-scientist))]

@Mercer

Selection would be stronger in the embryo than in the placenta.

Why would that be the case?

[Mercer (John Mercer)]

It’s a hypothesis, signaled by my inclusion of “would.”

This is how actual scientists converse, Valerie. The next step is to talk about the experiments one might do to test the hypothesis, that fun part of science.

There’s already a lot of sorting going on within the blastocyst, as only a small part of it actually becomes the embryo–the part from which we can isolate embryonic stem cells. Most of the blastocyst ends up as extraembryonic structures.

[sfmatheson]

@thoughtful

@Mercer

Selection would be stronger in the embryo than in the placenta.

Why would that be the case?

It’s a good question. I think one big reason (maybe the biggest) is that the embryo is expected to be much less tolerant of aberrant cells, because the embryo has the task of creating an organism. (Whereas the placenta is a big blob with a relatively straightforward set of roles. I hope placenta fans don’t get too upset by these comments.) Aneuploid cells show distorted gene expression and (as shown in a paper posted earlier in this thread) reduced growth overall. The reasoning, if I’m not mistaken, is that we don’t see many of those in embryos because embryos don’t get very far carrying aneuploid cells. @Mercer can expand or correct me if he has something else in mind.

[John_Harshman]

@Mercer

There’s already a lot of sorting going on within the blastocyst, as only a small part of it actually becomes the embryo–the part from which we can isolate embryonic stem cells.

Sure, but would you call that sorting? Are the various cells in the blastocyst arguing among themselves about which ones get to be part of the embryo? Are they sorting by karyotype? Or is it dependent on location? I really am not getting your selection scenario here.

[Mercer (John Mercer)]

@John_Harshman

Sure, but would you call that sorting? Are the various cells in the blastocyst arguing among themselves about which ones get to be part of the embryo? Are they sorting by karyotype? Or is it dependent on location? I really am not getting your selection scenario here.

I would suggest that much of it is just a race–if you look at the issues with the DS fibroblasts in that PNAS paper, aneuploid cells would be less likely to contribute, just on the basis of the metabolic demands for rapid division.

Of course, this is a gross oversimplification layered over the complexity of what is already known about sorting in the early embryo, for example:

https://www.pnas.org/content/107/14/6364

[John_Harshman]

@Mercer

I would suggest that much of it is just a race–if you look at the issues with the DS fibroblasts in that PNAS paper, aneuploid cells would be less likely to contribute, just on the basis of the metabolic demands for rapid division.

But aren’t placenta cells also undergoing rapid division?

[Mercer (John Mercer)]

That happens later, after the inner cell mass (the embryo itself) has been separated from the extraembryonic structures.