Cell Lineage Differentiation over Time, Space and Genome

Elucidating how the genome shapes the regulatory landscape of cell lineage differentiation is critical for our understanding of development and in vitro cell fate engineering. However, experimental data are scarce on in vivo lineage analysis with high temporal and spatial resolution. We have recently conducted a systematic study of lineage differentiation in the C. elegans embryo. We perturbed 204 conserved and essential genes across the genome by RNAi, and analyzed the lineage of 1,368 embryos by in toto imaging and direct cell tracking [1, 2]. The Digital Development database provides the platform to browse, search and download the results. Briefly, the dataset contains the following:
  1. 1,368 cell lineages coupled with tissue marker expression. All embryos showed the emb (embryonic lethal) phenotype, and the lineage was traced through the first 9 out of a total of 10 rounds of cell divisions to the 350-cell stage.
  2. 820 progenitor fate changes in essentially all lineage founder cells, each suggesting a cell-specific function of the corresponding gene in fate regulation. Notably, these include 175 regulatory switches of binary fate choices.
  3. A multiscale model that integrates 25 progenitor cell fates, 56 fate trajectories and 52 cell-specific gene networks.


  1. Du, Z, Santella, A, He, F, Tiongson, M, and Bao, Z. (2014). De novo inference of systems-level mechanistic models of development from live-imaging-based phenotype analysis. Cell, 156, 359-372.
  2. Du, Z, Santella, A, He, F, Shah, PK, Kamikawa, Y and Bao, Z. (2015). The regulatory landscape of lineage differentiation in a Metazoan embryo. Developmental Cell, 34(5), 592-607.