Out today in Cell: a comprehensive map of Human Accelerated Region gene targets in human and chimpanzee neural stem cells. Thread: https://t.co/w4hTXjbkrq https://t.co/r0ubl9PHou

@atreyop @noble_95 @BaumofLife Thanks also to the NOMIS Foundation and @NICHD_NIH for supporting this work!

@atreyop @noble_95 @BaumofLife As always, here is a link to the original preprint so you can see how the paper changed in revision: https://t.co/5TVvHN8c2q

@atreyop @noble_95 @BaumofLife Much more in the paper, including details on the Capture-C approach that enabled us to generate much denser and higher-resolution contact maps than had been possible in previous studies

Congratulations to @atreyop , our physicist-turned-neurogenomicist who led the experimental and computational arms of the project, and to co-authors @noble_95 , Matheo Morales, Richik Pal, @BaumofLife , Je Won Yang, Kristi Yim and Severin Uebbing

6. This included differentially expressed HAR targets that we could assign to outer radial glia, which are hypothesized to contribute to human cortical expansion

5. Important for understanding how HARs may have influenced human brain evolution: using single cell expression atlases of fetal human brain, we were able to identify the specific fetal brain cell types in which HAR targets are expressed

4. We do detect species-specific gene targets, but they did not converge on known biological functions and were not significantly enriched among differentially expressed genes, suggesting that HARs largely do not alter gene expression via enhancer hijacking

3. Conserved HAR gene targets are also enriched among genes differentially expressed between human and chimpanzee NSCs or between human and non-human primate developing and adult brain

2. These 2,963 "conserved" gene targets are highly enriched for neurodevelopmental processes including neurogenesis and synaptic transmission

1. HARs seem to act by altering the expression of the same genes their chimpanzee orthologs target - in other words, we don't find evidence supporting the recently proposed enhancer hijacking mechanism

You can find us going forward at that other blue-themed site

My top picks: Horwich/Hartl for their work on chaperone-mediated protein folding. Their discoveries changed how we think about protein structure and has had significant ramifications for our understanding of neurodegenerative diseases.

Happy to share this great review by co-authors @BaumofLife and Yu Ji on modeling human-specific regulatory functions in vivo, just out in Current Opinion in Genetics and Development! https://t.co/1eKwd6dEXF

I’m excited to share that I’m starting a new position as a Yale School of Medicine Science Fellow in the Department of Genetics @YaleGenetics! I’ll be co-mentored by the Reinke and @Noonanlab Labs. Can’t wait to join the scientific community at Yale this Sept! @YaleSciFellows

Thanks also to @SFARIorg and @SimonsFdn for supporting this work!

Thanks also to @KrishnaswamyLab and @david_van_dijk who developed one of the core methods we used in the paper, PHATE, and who helped with data analysis in the early stages of the project.

Congratulations to lead authors Kristi Yim, @BaumofLife and @MartinaKrenzer, and co-authors Maria Rosales Larios, Mina Hill-Teran, Tim Nottoli and @rebeccamuhle for their Herculean efforts to complete this project

So, Chd8 haploinsufficiency has complex effects, with distinct impacts in progenitors compared to maturing excitatory neurons.

In contrast, genes implicated in synaptic organization and activity were dysregulated in Chd8+/− postnatal day (P) 25 deep- and upper-layer excitatory cortical neurons, suggesting a delay in synaptic maturation or impaired synaptogenesis due to CHD8 loss of function.