Xiaoli Sky Wu

@xiaoliwu.bsky.social

Post doc with Mike E Greenberg at HMS, working on molecular neuroscience. Ph.D.at CSHL on identifying a novel family of cell type-specific cofactors. Co-organizer of Gene expression and RNA series, and Fragile nucleosome seminar.

If you're an international PhD student at Harvard working on something that my lab is familiar with and you're at risk of deportation, shoot me an email. We may be able to host you or find someone else who can.

Tomorrow!!! Register and join us for exciting research talks from @baluapuri.bsky.social and @juliecocquet.bsky.social!

FragileNucleosome@fnucleosome.bsky.social · last yr.

⚡Next Wednesday! In our next #FragileNucleosome seminar session, we are delighted to host, @baluapuri.bsky.social and @juliecocquet.bsky.social! If you've registered to one of our previous 2025 sessions, you can use the same link to join our next session. If not: us06web.zoom.us/webinar/regi...

We just posted two preprints on uncovering the genetic bases of species-specific differences in neural progenitors, excitatory neurons, and upon neuronal stimulation using the human-chimpanzee tetraploid system. Please check them out! www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1...

Human-chimpanzee tetraploid system defines mechanisms of species-specific neural gene regulation

A major challenge in human evolutionary biology is to pinpoint genetic differences that underlie human-specific traits, such as increased neuron number and differences in cognitive behaviors. We used human-chimpanzee tetraploid cells to distinguish gene expression changes due to cis -acting sequence variants that change local gene regulation, from trans expression changes due to species differences in the cellular environment. In neural progenitor cells, examination of both cis and trans changes – combined with CRISPR inhibition and transcription factor motif analyses – identified cis -acting, species-specific gene regulatory changes, including to TNIK , FOSL2 , and MAZ , with widespread trans effects on neurogenesis-related gene programs. In excitatory neurons, we identified POU3F2 as a key cis -regulated gene with trans effects on synaptic gene expression and neuronal firing. This study identifies cis -acting genomic changes that cause cascading trans gene regulatory effects to contribute to human neural specializations, and provides a general framework for discovering genetic differences underlying human traits. ### Competing Interest Statement C.A.W. is on the SAB of Bioskyrb Genomics (cash, equity) and Mosaica Therapeutics (cash, equity), and is an advisor to Maze Therapeutics (equity), but these have no relevance to this work. The remaining authors declare no competing interests.

biorxiv.org