Extended Data Fig. 9: Comparison of patterning variability in the presence and absence of morphogen treatment.
From: Systematic scRNA-seq screens profile neural organoid response to morphogens
a, Stacked barplots, showing the cell type composition of each condition for H1 (left), WTC (middle) and WIBJ2 (right)-derived organoids, split by experimental batches. Concentrations are indicated by c1-5, treatment time windows are indicated by t1-t5. Cell types colour codes are identical to panel b. b, Barplots (left) show total number of cells sequenced and percentage of cells in each cluster per condition in the morphogen reproducibility experiments. Heatmap shows enrichment (orange) and depletion (purple) of each cluster across conditions (right). All results are presented split by cell line. c, Boxplots showing distribution of percentage of progenitors, neurons and off-target cell types, split by neural induction approach, with the median indicated, where the boxes show the quartiles of the measurement and the whiskers, the 1.5 IQRs of the lower and upper quartile. NPC, neural progenitor cells; off, off-target cell types. Statistically significant compositional differences were estimated using a linear model, implemented in the speckle package, followed by 2-sided t-test. P-values were FDR adjusted using Benjamini-Hochberg procedure. Exact adjusted P-values are 0.28 NPC, 9.4*10-11 for Neurons and 3.3*10-5 for off-target. n = 48 for each category, samples being each organoid. d, Scatterplot showing enrichment of cell types over control for patterning reproducibility (y-axis) and patterning condition screen (x-axis) for WTC (left) and H9 (right) cell lines. Shape of the dot indicates the morphogen treatment condition, color indicates thecell type. Datapoints aligning with the diagonal represent treatments that are highly reproducible in the two screening setups. e, UMAP of the integrated human neural organoid cell atlas (HNOCA), colored by cell class (left) and brain region (right) as provided in the original publication. PSC, pluripotent stem cell; N.epith, neuroepithelium; NPC, neural progenitor cell; IP, intermediate progenitor; OPC, oligodendrocyte progenitor cell; CP, choroid plexus; EC, endothelial cell; NC, neural crest; MC, mesenchyme. f, UMAP of the integrated human neural organoid cell atlas, colored by the max presence scores across all control and treatment conditions in patterning reproducibility and patterning condition screen.
