Decoding transcriptional identity during Neuron-Astroglia Cell Fate driven by RAR-specific agonists
Description
How cells respond to different signals leading to defined lineages is an open question to understand physiological differentiation leading to the formation of organs and tissues. Among the various morphogens, retinoic acid signaling, via the RXR/RAR nuclear receptors activation, is a key morphogen of nervous system development and brain homeostasis. Here we analyze gene expression in ~80,000 cells covering 16 days of monolayer mouse stem cell differentiation driven by the pan-RAR agonist all-trans retinoic acid, the RAR-alpha agonist BMS753 or the activation of both RAR-beta and RAR-gamma receptors (BMS641+BMS961). Furthermore, we have elucidated the role of these retinoids for driving nervous tissue formation within 90 days of brain organoid cultures, by analyzing > 8,000 distinct spatial regions over 28 brain organoids. Despite a delayed progression in BMS641+BMS961, RAR-specific agonists led to a variety of neuronal subtypes, astrocytes and oligodendrocyte precursors. Spatially-resolved transcriptomics performed in organoids revealed spatially distinct RAR isotype expression leading to specialization signatures associated to matured tissues, including a variety of neuronal subtypes, retina-like tissue structure signatures and even the presence of microglia.
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Provided matrices are quantile normalized and corrected for image pixels intensity for reflecting for the presence/absence of cells across the tissue. Normalized matrices ca be visualized with Multilayer (https://github.com/SysFate/MULTILAYER) by uploading them as "raw matrix" but also as "Norm matrix" to avoid that the tool applies a quantile normalization processing. Provide images (in png format) are provided for comparison with the outcome produced by the matrices when loaded in Multilayer.