Single‐cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos

Abstract

Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems-level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage-dependent manner, with switch-like changes accompanying anterior-posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra-tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left-right symmetric pattern are predetermined to be analogous in early progenitors so as to pre-set equivalent states. Finally, genome-wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co-regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single-cell level.

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes

“…The applications of the approaches for and findings characterizing the cellular physiological states associated with cell shapes in this paper can be extended to many aspects: Regarding the specification of cell lineage and cell fate coupled with cell shape, systematic analysis of all cells and all stages throughout embryogenesis can be carried out beyond the representative studies of the MS and D lineages mentioned above ( Figure 6 and Figure 7 , respectively). Meanwhile, more public datasets, such as datasets on gene expression (measured by a fluorescence reporter and RNA sequencing) and chromatin accessibility, can be included [ 54 , 55 , 63 ] to systematically delineate how the developmental dynamics at the molecular scale affect those at the cellular scale which are depicted by different aspects of the cell shape, as well as those at higher scales such as tissue-, organ-, and embryo-scale morphogenesis. As the shape descriptors reported in this paper have explicit geometric significance and have been validated by specific physiological phenomena, they can be applied to the datasets of other organisms, such as ascidians, fruit flies, and zebrafish [ 9 , 10 , 64 ].…”

“…Regarding the specification of cell lineage and cell fate coupled with cell shape, systematic analysis of all cells and all stages throughout embryogenesis can be carried out beyond the representative studies of the MS and D lineages mentioned above ( Figure 6 and Figure 7 , respectively). Meanwhile, more public datasets, such as datasets on gene expression (measured by a fluorescence reporter and RNA sequencing) and chromatin accessibility, can be included [ 54 , 55 , 63 ] to systematically delineate how the developmental dynamics at the molecular scale affect those at the cellular scale which are depicted by different aspects of the cell shape, as well as those at higher scales such as tissue-, organ-, and embryo-scale morphogenesis.…”

A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis

“…Animals without the fluorescent co-injection markers that survived heat shock (34 °C for 2 h) were picked to a new plate, propagated, and genotyped to obtain homozygous transgenic strains. To overcome position effects on transgene expression 110 , 131 , at least two independent integration strains were obtained for each miRNA transcriptional reporter.…”

Live imaging of postembryonic developmental processes in C. elegans

“…The main limitations of this protocol are: (1) The protocol cannot be applied to the imaging of later embryonic development since worms begin to writhe within the eggshell in the later stages of embryonic development and could not be immobilized with anesthetic. The resources about live imaging of embryogenesis can be found in Wormbook or reported studies ( Bao and Murray, 2011 ; Laband et al., 2018 ; Zhao et al., 2021 ). (2) The physiological functions of C. elegans are affected after the imaging time longer than 4 h, leading to slowing down in the speed of cell division and migration, which is also reported elsewhere ( Chai et al., 2012 ).…”