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Abstract
The first meeting exclusively dedicated to the ‘High-throughput dense reconstruction of cell lineages' took place at Janelia Research Campus (Howard Hughes Medical Institute) from 14 to 18 April 2019. Organized by Tzumin Lee, Connie Cepko, Jorge Garcia-Marques and Isabel Espinosa-Medina, this meeting echoed the recent eruption of new tools that allow the reconstruction of lineages based on the phylogenetic analysis of DNA mutations induced during development. Combined with single-cell RNA sequencing, these tools promise to solve the lineage of complex model organisms at single-cell resolution. Here, we compile the conference consensus on the technological and computational challenges emerging from the use of the new strategies, as well as potential solutions.
Highlights
Similar to family trees, all cells in any multicellular organism are connected by a genealogical line that relates every cell to the first single cell in the organism
As dissociated cells are often subjected to single-cell RNA-Seq, their loss, which can be greater than 50%, can leave many gaps in the lineage reconstruction [25,26]
As to basic lineage topology, we propose a broad adoption of the convention used by the Drosophila community to refer to various asymmetric-division lineages as Type 0/1/2 lineages [63]
Summary
All cells in any multicellular organism are connected by a genealogical line that relates every cell to the first single cell in the organism (zygote). Despite the existence of many strategies for lineage reconstruction, this meeting focused on the deployment of emerging tools built upon recent advances from studies of natural somatic mutations [1,2] These tools use accumulated DNA mutations (CRISPR-induced in model organisms or natural mutations in human studies) to deduct cell lineage via phylogenetic analysis. This technology is powerful, in theory enabling the reconstruction of the lineage of any entire organism at single-cell resolution. In addition to its importance to our understanding of developmental biology, reconstruction of cell lineages can have an impact in the clinic and in other applications, such as cancer therapy or tissue engineering The advancement of this technology led to the choice of single-cell lineage reconstruction as a 2018 breakthrough of the year, by the journal Science
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