Single cell transcriptomic landscapes of pattern formation, proliferation and growth in Drosophila wing imaginal discs

Abstract

Organ formation relies on the orchestration of pattern formation, proliferation and growth during development. How these processes are integrated at the individual cell level remains unclear. In the past decades, studies using Drosophila wing imaginal discs as a model system have provided valuable insights into pattern formation, growth control and regeneration. Here, we provide single cell transcriptomic landscapes of pattern formation, proliferation and growth of wing imaginal discs. We found that patterning information is robustly maintained in the single cell transcriptomic data and can provide reference matrices for computationally mapping single cells into discrete spatial domains. Assignment of wing disc single cells to spatial subregions facilitates examination of patterning refinement processes. We also clustered single cells into different proliferation and growth states and evaluated the correlation between cell proliferation/growth states and spatial patterning. Furthermore, single cell transcriptomic analyses allowed us to quantitatively examine disturbances of differentiation, proliferation and growth in a well-established tumor model. We provide a database to explore these datasets at http:// drosophilayanlab-virtual-wingdisc.ust.hk:3838/v2/. This article has an associated 'The people behind the papers' interview.

Single-cell transcriptomics of theDrosophilawing disc reveals instructive epithelium-to-myoblast interactions

“…The few tracheal cells were identified by high expression of the genes waterproof (wat) and tracheal-prostasin (tpr) (Jaspers et al, 2014;Drees et al, 2019), and the hemocytes were distinguished by high expression levels of Hemese (He) and regucalcin (Kurucz et al, 2003;Klebes et al, 2005) ( Figure 1E, Figure 1 -figure supplement 1). We observed a similar set of marker genes as other recently published wing disc scRNAseq analyses (Deng et al, 2019;Bageritz et al, 2019;Zappia et al, 2019). Altogether, we recovered profiles for 19,885 adult muscle precursors (AMPs), 7,104 wing disc epithelial cells, 15 tracheal cells, and 12 hemocytes.…”

“…Single-cell transcriptomics provides a powerful paradigm for mapping the cellular composition of developing organs (Schier, 2020), including vertebrate appendages (Fabre et al, 2018;Cao et al, 2019;Feregrino et al, 2019), and has been successfully utilized for characterizing the Drosophila wing disc at single snapshots during development (Deng et al, 2019;Bageritz et al, 2019;Zappia et al, 2019). Beyond cataloging cell types, transcriptomescale analysis of single cells opens the way for a comprehensive evaluation of how interactions between cells may facilitate development (Satija et al, 2015;Karaiskos et al, 2017;Deng et al, 2019;Bageritz et al, 2019). Analysis of cell-cell interactions in this context can benefit greatly from information about the physical organization of the tissue in question, and particularly the position of different cell types in the tissue.…”

“…Analysis of cell-cell interactions in this context can benefit greatly from information about the physical organization of the tissue in question, and particularly the position of different cell types in the tissue. Since in most prevalent protocols this information is lost, computational methods are used to infer it, usually based on the expression of landmark genes (Satija et al, 2015;Karaiskos et al, 2017;Deng et al, 2019;Bageritz et al, 2019).…”

A single-cell transcriptome atlas of the adult muscle precursors uncovers early events in fiber-type divergence inDrosophila

“…Together with two recent studies (Bageritz et al, 2019;Deng et al, 2019), our work provides a valuable resource for the Drosophila community as a part of The Fly Cell Atlas initiative (https://flycellatlas.org/). The second conclusion of our work is that the populations of IFM and DFM precursors are highly heterogeneous as we identified five IFM and two DFM clusters that represent cells at various states of differentiation.…”

Model systems for regeneration: Drosophila

“…Moving forward, new precision injury tools in both established and new tissue regeneration models can lead the way. Other promising approaches, such as live imaging of intact adult midgut tissue (Martin et al, 2018), high-resolution chromatin mapping in imaginal discs (Uyehara et al, 2017;Vizcaya-Molina et al, 2018) and single-cell sequencing (Deng et al, 2019) will also help uncover new regeneration biology. Given the genetic prowess and the tools now available in this model, Drosophila will be a major player in the regeneration field for decades to come.…”