De Humani corporis fabrica:replaying Vesalius through brain organoids at single cell omic resolution

Date

Nov 26, 2020

Time

11:00 AM - 12:00 PM

Speaker

Giuseppe Testa

Affiliation

University of Milan & Human Technopole, Milan, Italy

Series

MPI-CBG Thursday Seminar

Language

en

Main Topic

Biologie

Host

Wieland Huttner/Nereo Kalebic

Description

In vitro models of human development are transforming biomedicine by making the developmental potential of individual genomes experimentally tractable. For developmental disorders as well as for late-onset disorders with an early developmental seeding, this patient-specific re-enactment of development promises to bridge altered developmental trajectories to clinical phenotypes at unprecedented resolution, especially through the pairing of single cell multi-omics with digital phenotyping. With the increasing scalability of in vitro organoidogenesis, the prospect is thus within reach for a systematic exploration, including a mechanistic dissection, of how genetic variation shapes the human developmental space, an intellectual pursuit with far reaching implications that requires scientific as well as ethical benchmarking. Here I lay out the principles for such benchmarking, starting from our most recent modelling of a particularly informative set of neurodevelopmental disorders caused by point mutations or dosage imbalances in chromatin regulators that operate in inter-related pathways. I present our single-cell level deconvolution, in brain organoids, of dosage-dependent alterations in developmental pathways along with a transcriptome-based benchmarking that allows us to empirically assess how far different paradigms of brain organoidogenesis recapitulate human brain development and match specific experimental needs. This benchmarking pipeline is then applied to the quest for convergent dysregulation across neurodevelopmental disorders and to multiplexed designs, experimental and computational alike, in order to advance the field towards population-level scalability

Last modified: Nov 27, 2020, 12:09:13 AM