The single cells of the developing human embryo are kinda awesome, but maybe they’ve grown a tad arrogant, perhaps a little “too cool for school”? They always hang around alone or in small cliques of similar cells, while the hippest scientists have only recently developed techniques, such as scNOMe-seq and scNMT-seq, trendy enough to begin to interrogate their small number!
To give these cells a schooling, a humble new study led by Fuchou Tang and Jie Qiao (Peking University, Beijing, China) has brought these superior-feeling cells back down to earth and revealed many of their tightly guarded secrets. Specifically, Li and colleagues employed their previously developed single-cell chromatin overall omic-scale landscape sequencing (scCOOL-seq!) technique to simultaneously assess several layers of epigenetic information in the developing human embryo. Of note, this stylish strategy enables the discrimination of aneuploid (chromosomally abnormal) cells from euploid (normal) cells and thereby strengthens the studies detailed results concerning chromatin state, nucleosome positioning, and DNA methylation.
Cool story so far; but, can you scCOOL-seq us on the details?
- Oocytes display a more open chromatin landscape than sperm, and fertilization leads to drastic chromatin remodeling and an overall reduction in chromatin accessibility until the 8-cell stage embryo
- Following zygotic gene activation, chromatin accessibility rises to a maximum value in the morula stage embryo (16-cell stage)
- Comparisons to mouse data concerning chromatin accessibility dynamics suggest species-specific features
- Genomic regions with the strongest variations in chromatin accessibility locate to proximal and distal nucleosome-depleted regions (NDRs) and pluripotency master transcription factor-binding regions
- This intrinsic feature may contribute to highly flexible cell fate determination in individual blastomeres
- Simultaneous analysis of DNA methylation alterations indicates that genes with heterogeneous chromatin accessibility differ from genes displaying heterogeneous DNA methylation during preimplantation development
- The study also discovered evidence for a feedback mechanism between transcription and open chromatin maintenance, as 35% of “widely-open” chromatin regions in promoters closed following inhibition of transcription
The authors suggest that the continued development of advanced multitasking small-input volume techniques to decipher how the many layers of epigenetic regulation change and interact will allow for decreased costs, increased mapping rates, and improved uniformity of coverage, thereby permitting researchers to achieve high confidence conclusions.
Now that the epigenetics of human embryos is no longer too cool for school see Nature Cell Biology, June 2018.