Search bioRxiv⌕ Search

Biology subjects

Galindo-Albarran, A.

Publications and source records attributed to Galindo-Albarran, A..

2 recordsLinked to original sources

Enhancing spatial omics resolution by pseudo-interstitial pixels inference

MotivationSpatially resolved omics technologies are enhancing our understanding of tissues architecture. Despite major technological improvements, gaining in spatial resolution becomes experimentally expensive, while generating spatial landscapes at moderate resolution combined with computational methods for depixelating data represent a cost-effective strategy allowing to enlarge the number of experiments to be performed. ResultsWe have developed a computational strategy able to gain several-folds of resolution by inferring pseudo-interstitial pixels from their closest neighbors. This strategy has been validated in the context of public spatial transcriptomics data issued from melanoma, and human brain cortex tissue sections, by improving the identification of distinct tissue substructures. Furthermore, this methodology has been used for enhancing the resolution of consecutive sections collected from human brain organoids, as a way to demonstrate that a moderate resolution technology, combined with spatial depixelation processing allows to properly discern molecular tissue structures even in small tissues. Contactmmendoza@genoscope.cns.fr

bioinformatics↗

Decoding transcriptional identity during Neuron-Astroglia Cell Fate driven by RAR-specific agonists

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 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.

systems biology↗