Transcriptional Regulation and Genes Involved in First Lineage Specification During Preimplantation Development
CHROMATIN REGULATION OF EARLY EMBRYONIC LINEAGE SPECIFICATION
Authors: Cui, Wei; Mager, Jesse
Abstract
The successful development from a single-cell zygote into a complex multicellular organism requires precise coordination of multiple cell-fate decisions. The very first of these is lineage specification into the inner cell mass (ICM) and trophectoderm (TE) during mammalian preimplantation development. In mouse embryos, transcription factors (TFs) such as Oct4, Sox2, and Nanog are enriched in cells of ICM, which gives rise to the fetus and yolk sac. Conversely, TFs such as Cdx2 and Eomes become highly upregulated in TE, which contribute to the placenta. Here, we review the current understanding of key transcriptional control mechanisms and genes responsible for these distinct differences during the first cell lineage specification. In particular, we highlight recent insights gained through advances in genome manipulation, live imaging, single-cell transcriptomics, and loss-of-function studies.
Network Analysis Reveals Centrally Connected Genes and Pathways Involved in CD8(+) T Cell Exhaustion versus Memory
IMMUNITY
Authors: Doering, Travis A.; Crawford, Alison; Angelosanto, Jill M.; Paley, Michael A.; Ziegler, Carly G.; Wherry, E. John
Abstract
Exhausted CD8(+) T cells function poorly and are negatively regulated by inhibitory receptors. Transcriptional profiling has identified gene expression changes associated with exhaustion. However, the transcriptional pathways critical to the differences between exhausted and functional memory CD8(+) T cells are unclear. We thus defined transcriptional coexpression networks to define pathways centrally involved in exhaustion versus memory. These studies revealed differences between exhausted and memory CD8(+) T cells including the following: lack of coordinated transcriptional modules of quiescence during exhaustion, centrally connected hub genes, pathways such as transcription factors, genes involved in regulation of immune responses, and DNA repair genes, as well as differential connectivity for genes including T-bet, Eomes, and other transcription factors. These data identify pathways involved in CD8(+) T cell exhaustion, and highlight the context-dependent nature of transcription factors in exhaustion versus memory.