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I recently came across an article about the fact that cell-lines provided by merchant entities to give cells to researchers, were tagged by ethnic origin. The article especially speaks about ethnic origin of African and European. The article points out that the lack of diversity in available cells has consequences on the effect of the therapies made by researchers, since they can work only on limited European (which are the majority of the provided cells). I understand that this concerns stem cells (am I correct?).

I understand of course the problem, but what remains unclear to me is : How are cells different depending on the ethnic origin? (especially protein coats of the cells that affects the vulnerability to diseases) The first answer I have is that they could be distinguished by their DNA (obviously genes coding skin color will be different).

With my researchs I found other articles that gave some information:

  • This lacks of diversity has an impact on the prostate cancer, so does it mean that prostate cells are different depending on the ethnic origin?
  • Some viruses have different expression in different ethnic origins
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The article is particularly concerned with personalized/precision medicine: tailoring therapy to specific individuals based on their genetic background.

The article is in particular talking not about stem cell lines, but about cell lines derived from patients with cancer. These cell lines are studied to understand what made those cells cancerous, to both understand mechanisms of cancer and develop treatment.

How are cells different depending on the ethnic origin?

The issue raised is not a specific difference, but rather the unknown. If you only study variation among European-derived cell lines, you cannot possibly understand human-wide variation. Further, if you have just one cell line labeled as "African-American" and use studies with this cell line to make decisions about how you're going to treat all Americans with Black/African ancestry, and that one cell line is also mostly of European origin, you shouldn't expect that research to result in good outcomes for African-American/Black patients.

An example of how this might work is that a bunch of study into cancer cell lines identifies some specific mutation associated with cancer, and some pharmaceutical treatment that is highly effective in cancers based on that mutation (perhaps an antibody-based treatment). The next step would be to identify patients who carry that specific mutation or where that mutation is present in biopsied tissue, to give them that customized therapy. However, if all the cell lines you study come from people with European ancestry, only people with European ancestry are likely to have any of those specific mutations, and everyone else is left out.

In particular, African populations are more genetically diverse than populations anywhere else, presumably because humans first evolved in Africa and subsequently traveled elsewhere. Therefore, studying mostly people of European ancestry merely because they are the dominant group in a specific high-wealth country like the US is leaving the majority of human genetic diversity out of study.

The article you linked about prostate cancer seems like a good place to further understand this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219314/

It describes how therapies developed because they are effective in a single prostate cancer line didn't actually work for most people with prostate cancer, and that subsequent efforts to study therapies in multiple cell lines have not benefitted "Men of African Ancestry" because those cell lines are predominantly derived from "Men of European Ancestry".

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  • $\begingroup$ Can you clarify how it comes about that "you have just one cell line labeled as 'African-American'...and that one cell line is also mostly of European origin"? Is it typical or atypical for a cell line from a random African-American patient to be "mostly of European origin"? Are you alluding to a specific cell line (e.g., HeLa)? I do see mention that Lacks's family was mixed-race ("Many of the black Lacks family were also descendants from the white Lacks family"). If that is your point, perhaps you can say it more directly. $\endgroup$
    – nanoman
    Jan 4, 2023 at 13:17
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    $\begingroup$ @nanoman This is from the article in OP's question, which links to this paper: aacrjournals.org/cebp/article/28/6/1003/71948/… "For instance, the 22Rv1 prostate cancer cell line was recently found to carry mixed genetic ancestry using a much smaller panel of markers. However, our more comprehensive analysis determined the 22Rv1 cell line carries 99% EUR ancestry. Most notably, the E006AA-hT prostate cancer cell line, classified as African American, was found to carry 92% EUR ancestry" $\endgroup$
    – Bryan Krause
    Jan 4, 2023 at 13:45
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    $\begingroup$ @nanoman Here's another descriptive article you might be interested in: cen.acs.org/biological-chemistry/cancer/… Overall, though, my answer isn't particularly concerned with testing the premise, and cancer biology or ancestry determination are not my fields. I'm just answering OP's question about why someone would find this concerning and what the implications are for personalized medicine. $\endgroup$
    – Bryan Krause
    Jan 4, 2023 at 13:54
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    $\begingroup$ @totalMongot "I suppose it is because ... this difference is already a known phenomenon" I disagree - the issue is if you don't study both you don't know what the differences are, plus that it is known that there are poorer outcomes for prostate cancer for Black patients. I don't understand your statement "why does'nt it impact viruses or bacteria the same way", my answer does not mention viruses or bacteria. $\endgroup$
    – Bryan Krause
    Jan 4, 2023 at 19:41
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    $\begingroup$ @totalMongot What do you mean by "a specific ethnic criteria"? A historical example might include the decimation of populations native to the Americas after exposure to European illnesses, notably smallpox. Sickle cell trait would be another example. $\endgroup$
    – Bryan Krause
    Jan 5, 2023 at 19:39
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To supplement @Bryan Krause's excellent answer, I would add another with a very specific example of the kind of variation that could affect research.

Different people have very different responses to drugs, and in many cases this variation is genetic. This variation exists across human populations, but can also to some extent be non-uniform or "private" to specific populations, meaning that sampling populations unevenly will give an inaccurate estimate of drug response variation. For example, appropriate warfarin dosing varies dramatically across patients, based in part on genetic variation in known genes.

Thus, if all cell lines tested for response to a new drug candidate are of European descent, then you only understand the pharmacokinetics of that drug for a relatively small sample of overall human pharmacokinetic variation. This could lead to ineffective or lethal (!) drug dose guidance if initial studies in cell lines do not assay a representative range of human genetic variation. (Note: in general, many regulatory safeguards are in place hoping to prevent this kind of event.)

Expert reviews have in some cases explicitly counseled personalized genetic testing to avoid such adverse drug reactions. This indicates that surveys at the population level are in fact inadequate to this problem, as they are too crude. So the issue is not really ethnic population representation, but rather the large scope of human genetic variation, to which apparent/reported ethnicity is only modestly correlated.

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Many of the works on "ethnic origin" are based on the chromosome Y. Majority of it (not all) does not have the pair to recombine (very small region still recombines with X), so essentially the same Y chromosome is passed from father to son, different only by infrequent mutations. Using these mutations, it is possible to construct a map of human origins, starting from Y-chromosomal Adam. This would reflect the history about how humans migrated, populating the Earth. The known "versions" of the Y chromosome are called "haplogroups", these are highlighted here by color (image credit):

enter image description here

There are obviously less groups than countries but very approximately this can be matched to the "ethnic origin" in cases like at least Russia, China, India or Australia, and to some ethnic groups that are known to be somewhat tied together, like the European region, for instance. In such cases, the origin of the parent line of ethnicity like Russian vs Ukrainian can be estimated by DNA sequencing of the Y chromosome.

These chromosome signatures cannot be "assimilated" by living for generations in a region where another type of Y is dominant. A hundred generations can pass and the simple scan of the Y chromosome would still show the true origins of the parent line.

There is obviously no reason to think that any version of Y chromosome is better than other. In general there not so many genes there. However anyway the Y chromosome is part of the cell.

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    $\begingroup$ The paper referenced in the OP's link is using SNPs from modern populations; so, if you have SNPs that are commonly found in people from Europe, and not commonly found in people elsewhere in the world, you can say you have a high probability of European ancestry. It's the same approach that commercial genome analysis companies offer to individuals. It has nothing to do with the Y chromosome or determining the migration of peoples in history/human origins. This answer also doesn't appear to answer the question asked about how the cells differ/what the concern is in this paper. $\endgroup$
    – Bryan Krause
    Jan 4, 2023 at 15:02
  • $\begingroup$ Please read the referenced sources, "has nothing to do with Y chromosome" $\endgroup$
    – h22
    Jan 4, 2023 at 15:24
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    $\begingroup$ @totalMongot no, ethnic differences are evenly spread over all chromosomes. $\endgroup$
    – user438383
    Jan 4, 2023 at 20:00
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    $\begingroup$ @h22 I honestly don't see how this answer addresses the question at all. OP was not asking about Y-Adam or the origin of ethnic differences at all. $\endgroup$
    – MattDMo
    Jan 4, 2023 at 21:23
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    $\begingroup$ Y haplogroups are good for tracking migration because they're strictly divergent (two Y hapologroups will never merge) and because they accumulate mutations at a predictable rate, giving information about timing. They're not much good for anything else precisely because of that divergence: every other chromosome can get mixed up with others. For example, an African-American male might be Y-hapologroup B-M150 (west African) with the entire rest of his DNA being European-typical variants. $\endgroup$
    – Mark
    Jan 5, 2023 at 2:11

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