What studies have been undertaken to discover stem cells?
This type of study was done on hematopoietic stem cells (the stem cells that will eventually become all the different blood system cells), and the study concluded that the traditional view of the differentiation from hematopoietic stem cells to T cells, B cells, macrophages, etc., is not supported by this new scRNAseq lineage study. Additionally, many views of lineages are created under the prediction that cells have a binary fate decision, but scRNAseq is opening the idea that progenitor populations are in fact heterogeneous, and that the differentiation comes from that pre-existing heterogeneity. An additional study found that the markers for the three preimplantation mammalian embryo lineages express themselves even before lineage maturation, supporting the idea of progenitor heterogeneity. These questions, however, are not settled.
Other studies have been undertaken that are smaller in scope but no less exciting. There is hope that gene regulatory networks will greatly benefit from scRNAseq, but as of yet the limitations of scRNAseq, particularly the low sensitivity for genes with low transcription rates, don’t pose that as a viable option. Another very exciting study discovered the exact stage of human and mouse development where zygotic gene activation occurs. Interestingly, the mouse ZGA happens significantly earlier in development than human ZGA, currently with no known reason. scRNAseq also confirmed the exact moment of blastomere asymmetry, but again, with no understanding as to the mechanisms of how this occurs. scRNAseq also facilitated the discovery of the prevalence of genome-wide allelic exclusion on a per cell basis. Finally, scRNAseq allowed insights into the Janus progenitor state, where a progenitor of two different cell types will express the markers of both of its progeny. It was these smaller scale discoveries that led me to see the pattern of current scRNAseq technology, where the really illuminating ‘what’ (the moment of ZGA and blastomere asymmetry, the new Janus state), but not yet allowing us to understand the ‘how.’ I am confident it will come in time, but for now, the collection of the ‘what’ is thoroughly exciting.