Nature 2021; 592: 8085https://www.nature.com/articles/s41586-021-03345-1
These authors performed whole-genome sequencing (WGS) of 86 bulk placental samples and of 106 microdissections of placental tissue in order to reconstruct the development of human placental cells from data on somatic mutations. They found that the placenta comprises of multiple very large, genetically distinct, clonal expansions (i.e. tissues derived from a single cell line) and that the cells carry a huge mutation burden, similar to that found in childhood cancers.
Abnormalities in placental development underlie the major disorders of pregnancy, preeclampsia, fetal growth restriction and stillbirth (1). Hence, understanding this process and the possible errors has important clinical relevance. Using a large scale WGS approach, the authors show that the placenta is an extreme outlier in terms of its high frequency of somatic mutations, compared to other healthy human tissues. Furthermore, these mutations do not appear to correlate with any functional segregation, as seen in other tissues (e.g. colonic crypt are clonal expansions within the gut). Rather, the pattern of mutations reflects the placental tree-like growth and anatomical structure, with each branch descending from a single cell with its own distinct somatic mutation fingerprint. The authors conjecture that the very rapid growth rate of the placenta compared to other tissues, increasing 3-fold between 8 and 12 weeks gestation, and its temporary existence, mean that these cells bypass the key mechanisms that typically protect against and remove DNA replication errors. We learn from these findings that, in the search for the placental changes that underlie major pregnancy disorders, genetic aberrations will not be uniformly distributed throughout the placenta, and this may explain inconsistencies in the findings of previous more limited studies.
Reference: 1. Brosens, I., Pijnenborg, R., Vercruysse, L. & Romero, R. The Great Obstetrical Syndromes are associated with disorders of deep placentation. Am. J. Obstet. Gynecol. 204, 193201 (2011).