As workers with stem cells know, human cells lines, whether they are embryonic or induced pluripotent, can develop into a wide variety of cells or tissues in the body. Now researchers at Boston Children’s Hospital have discovered that stem cells that express a gene called WNT3 are biased to develop into cell and tissues of the pancreas, liver and bladder. This suggests that other genes may be biomarkers for stem cells with preferences for turning into other tissue types. If so, markers such as this would make it easier for stem cell scientists to choose the right cell line when they want to generate specific tissues.
Genes May Bias Stem Cell Development
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According to the Boston Children’s press release, Wei Jiang and Yi Zhang, both Ph.D.s, led the study and published their findings in the journal Stem Cell Reports. Zhang said, “If you want to differentiate stem cells into pancreas cells, for instance, you want to start with a line with a high differentiation potential for endoderm. It’s like athletes and sports. Some athletes are built for football, some for baseball, and some for swimming. Every cell line has its own strengths, and the challenge is knowing what those strengths are.”
Currently, investigators must test several lines with the same differentiation process—which can take a great deal of time and effort—and then use the one that turns out to be the most efficient at producing cells of the type they need. What they would like to be able to do, Zhang says, “is select the most appropriate cell line without having to carry out full differentiation experiments first.”
How WNT3 affects endoderm differentiation potential is not yet clear, and is something Zhang wants to understand. But he believes that other genes may possibly serve as markers for selecting lines primed for mesoderm and ectoderm development. “We would like to find other markers and develop a scoring system, ” he said. “There are many hESC and iPSC lines, and we need a simple way to tell which to use in order to produce particular cell types.”
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This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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