Chimeras

We will be hearing more and more about chimeras.  In genetics, a chimera is an animal that has two or more different populations of genetically distinct cells that originated in different zygotes(ref).    The word was adopted from Greek mythology where the description is more colorful and gets down to the nitty-gritty.  According to Wikipedia  “the Chimera (Greek Χίμαιρα (Chímaira); Latin Chimaera) was a monstrous fire-breathing creature of Lycia in Asia Minor, composed of the parts of multiple animals: upon the body of a lion with a tail that terminated in a snake’s head, the head of a goat arose on its back at the center of its spine. The Chimera was one of the offspring of Typhon and Echidna and a sibling of such monsters as Cerberus and the Lernaean Hydra.”  Get the idea?

The news this week was two reports from Chinese researchers of making chimeric mice using induced pluripotent stem cells (iPSCs).  The mice were made by taking skin cells from mice, reverting these cells to iPSC status where they become virtually identical to embryonic stem cells (see the blog post Rebooting cells and longevity), and injecting them back into into eary-stage mouse embryos.  On of the reasons this work is important is that it established the true pluripotency of the iPSCs used.  After all, if you can make a whole living mouse out of them, they must be capable of differentiating into any mouse tissue.  “The generally accepted “gold standard” for determining whether a mouse iPSC line has been fully reprogrammed is to show that when injected into an early embryo (or blastocyst), the iPSCs can contribute to many different tissues in the resulting chimeric mouse, including the germline(ref).”  One of the chimeric mice made this way is reported to have mated with a normal mouse resulting in the birth of a normal mouse pup. Of course this is all on the level of the mouse.  Ethical and legal considerations are in the way of making chimeric “designer people,” but the results still give hope that iPSCs can be used for any purpose embryonic stem cells (eSCs) could be used for.

However, other stem cell research reported earlier this month indicates that the gene expression profiles of iPSCs and eSCs are different.  The study compared eSCs and iPSCs made by reprogramming skin cells. “The data from the study suggest that embryonic stem cells and the reprogrammed cells, known as induced pluripotent stem (iPS) cells, have overlapping but still distinct gene expression signatures. The differing signatures were evident regardless of where the cell lines were generated, the methods by which they were derived or the species from which they were isolated(ref).”  The researchers do not know what the practical implications of this finding are.  Whatever they are, they seem to be not enough to get in the way of making whole living chimeric mice. 

Chimeras, hybrid animals, have been around for some time and are interesting curiosities. According to Wikipedia “Chimeras are formed from four parent cells (two fertilized eggs or early embryos fused together) or from three parent cells (a fertilized egg is fused with an unfertilized egg or a fertilized egg is fused with an extra sperm). Each population of cells keeps its own character and the resulting animal is a mixture of tissues.”  Moreover people may be chimeras and not know it.  “As the organism develops, the resulting chimera can come to possess organs that have different sets of chromosomes. For example, the chimera may have a liver composed of cells with one set of chromosomes and have a kidney composed of cells with a second set of chromosomes. This has occurred in humans, and at one time was thought to be extremely rare, though more recent evidence suggests that it is not as rare as previously believed. Most will go through life without realizing they are chimeras. The difference in phenotypes may be subtle (e.g., having a hitchhiker’s thumb and a straight thumb, eyes of slightly different colors, differential hair growth on opposite sides of the body, etc) or completely undetectable . Another telltale of a person being a chimera is visible Blaschko’s lines(ref).”