Our paper looking at the long-term maturation of cortical organoids is out! rdcu.be/cfDQt #organoids #brainorganoids

TL;DR - human cortical organoids start to resemble postnatal cortical development after 250-300 days of culturing
This work was a great collaboration between @GeschwindLab @PascaStanford @gracexiao99 and @HuguenardLab. Thank you to all coauthors @SeJinYoon3, Sthephan Tran, @MakinsonLab, @jimena_andersen, @FreddyMValencia and Steve Horvath
In this project, we generated human cortical organoids from 6 human iPSC lines and grew them for up to 694(!) days
We found that based on an unbiased genome-wide approach taking into account all the changes in gene expression across time, cortical organoids start to look like postnatal brain after 250-300 days of culturing
Seeing a strong similarity between organoids and the developing brain, we compared the biological processes between these two systems and found that many of the processes that occur during cortical development are preserved in the organoids
We found that RNA editing which is dynamically regulated during development, is also partially preserved in these cortical organoids
To explore prenatal to postnatal transition in the organoids we looked at gene changes that occur around birth such as NMDA receptors NR2A/B that switch around birth in the developing cortex and found the same switch in the organoids at around 250 days.
Looking at the expression of genes associated with many neurodevelopmental and neurodegenerative disorders we found that these genes clustered into distinct groups based on when they were expressed.
At least one of these clusters in each disorder peaked in expression after 250 days of differentiation suggesting that longer differentiation will be needed to study these genes.
We provide a web tool – GECO – which allows for a detailed comparison of gene expression between cortical organoids and the developing cortex
This work was made possible by funding from @CIRM @NIMHgov @BBRFoundation @AutismScienceFd @NSF @nyscf @czi

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More from @Aaron_Gordon1

29 Sep 20
It’s out! “Neuronal defects in a human cellular model of 22q11.2 deletion syndrome” in which we used 3D human cortical spheroids neurons to study the pathways linked to neuropsychiatric disease in 22q11.2 deletion. rdcu.be/b7N8D
This work was a great collaboration with my co-first authors @themasap and @omerevah. A result of a vast collaboration between @PascaStanford @GeschwindLab @HuguenardLab @rdolmetsch @Winkytheelf, Porteus, Nishino, and Hallmayer labs.
22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. 1 in 4 22q11.2DS patients develop psychosis,
which corresponds to a 20-fold increase in risk and accounts for 1–2% of all SCZ cases.
Read 12 tweets
2 May 19
Super excited to post my first preprint and first lead author paper from the Geschwind lab in which we used expression networks to find neuronal energetic to be abnormal across three mice model of psychiatric disorders. Thread to follow. 1/
We examined the cortical and hippocampal transcriptome in three mouse models of psychiatric disorders 15q13.3 deletion, 1q21.1 deletion and 22q11.2 deletion. Initial differential expression didn’t uncover any points of convergence between the different mouse models. 2/
Using co-expression networks (WGCNA) we discovered a module dysregulated across the different mouse models which was linked to neuronal mitochondrial function and more specifically to the energetics of firing rates in inhibitory neurons. 3/
Read 4 tweets

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