Alex Pollen

Alex Pollen

@brainevodevo.bsky.social

Studying specializations and vulnerabilities of human brain development

1.2K followers146 following46 posts

Alex Pollen reposted

🦴✨ Invited speaker Douglas B. Menke joins us at #2026SDB in Las Vegas! 🎰 His lab explores how vertebrate limb morphology evolves through changes in gene regulation 🧬🐭 with current work focused on Tbx4 enhancer elements that shape hindlimb development and evolution across species. 🐾✨ #evodevo

7/ We found a postmitotic role for ARX in safeguarding interneuron identity. Without ARX, the cells display “ectopic" subtype identity, characterized by LMO1 upregulation.

5/ We also identified NR2E1 and ARX that have opposing roles in regulating the balance of excitatory versus inhibitory neurogenesis. By combining single cell lineage tracing with Perturb-seq, we discovered their roles in balancing RG lineage plasticity and progression.

6/ Multiple transcription factors converge on shared downstream targets - these hub effector genes are often linked to neurodevelopmental and neuropsychiatric disorders, suggesting disorder related genes are more well connected in the TF regulatory networks.

2/ Radial glia are multipotent progenitor cells that give rise to most cells in the cortex, including excitatory neurons, oligodendrocytes and astrocytes, as well as olfactory bulb interneurons and a recently characterized population of cortical interneurons.

Alex Pollen reposted

A deep dive into how transcription factors shape radial glia fate and clonal dynamics. Manuel Lessi: this work “combines the strengths of primary cultures and pooled CRISPRi perturbation”. #preprint Jingwen Ding & team @brainevodevo.bsky.social #preLight ⬇️ prelights.biologists.com/highlights/d...

prelights.biologists.comDissecting Gene Regulatory Networks Governing Human Cortical Cell Fate - preLightsA deep dive into how transcription factors shape radial glia fate and clonal dynamics

Collectively, the broad pattern of inhibitory neuron conservation suggests that, on the mammalian timescale, evolution modifies the brain by ‘teaching old cells new tricks’, rather than inventing novel cell types early in development.

In adult mouse, we identified a rare subpopulation of Th interneurons which expresses residual Tac2 (TAC3). Using the Allen institute’s Merscope data, we find this rare Tac2-expressing population is spatially restricted to the ventromedial striatum.

Surprisingly, we find that the population was hiding in plain sight, but disguised by the loss of TAC3 (called Tac2 in mouse) and gain of Th expression, indicating an unappreciated homology between rodent Th and mammalian TAC3 striatal interneurons.

Through integrated analysis of adult mouse, marmoset, and human striatal inhibitory neurons, we confirmed the homology of Th interneurons in adult mouse and TAC3 interneurons in the adult primate.

Although the TAC3 initial class is conserved to marsupials (opossum and sugar glider), we observe turnover of signaling pathway genes across multiple timescales, and an additional migratory destination in Laurasiatherian (pig and ferret) cortex

Given the conservation of this initial class in Laurasiatherians and marsupials, we next investigate the Glire lineage (rabbit, naked mole rat, rat, mouse), as the population was reported missing in mouse.

We begin by performing cross-species analysis of developing initial classes of both striatal and cortical inhibitory neuron populations by integrating single cell sequencing data from 8 mammals, spanning from primates to marsupials.

Through integrative analysis, we find that initial classes of inhibitory neurons are conserved across placental mammals. Surprisingly, this conservation includes the MGE-derived TAC3 initial class, which was previously thought to be a primate-specific striatal interneuron population

Alex Pollen reposted

🧠🌟🐭 Excited to share some of my postdoc work on the evolution of dexterity! We compared deer mice evolved in forest vs prairie habitats. We found that forest mice have: (1) more corticospinal neurons (CSNs) (2) better hand dexterity (3) more dexterous climbing, which is linked to CSN number🧵

bioRxiv Neuroscience@biorxiv-neursci.bsky.social

Evolutionary expansion of the corticospinal system is linked to dexterity in Peromyscus mice https://www.biorxiv.org/content/10.1101/2025.10.16.682851v1

Alex Pollen reposted

I am thrilled to share our latest work: we identified a population of central amygdala neurons that promote the earliest and perhaps most important social behavior: pup suckling!... We also developed new tools for pup neuroscience Work by @Jeff Moore now at USC, a collaboration with @Sam Pfaff lab

bioRxiv Neuroscience@biorxiv-neursci.bsky.social

A genetically-defined population of amygdalofugal neurons promotes suckling and early postnatal growth https://www.biorxiv.org/content/10.1101/2025.10.18.683193v1

Alex Pollen reposted

Alex Pollen reposted

"Sources said the administration is specifically considering a full termination of federal grant funding for the University of California and California State University systems." Pure vandalism. This could never happen in a country with functioning checks and balances.

cnn.comTrump preparing large-scale cancellation of federal funding for California, sources say | CNN PoliticsThe Trump administration is preparing to cancel a large swath of federal funding to California, an effort which could begin as soon as Friday, according to multiple sources.

Alex Pollen reposted

Congratulations to Nathan for conceiving and designing this unified demultiplexing toolkit!

Nathan Schaefer@nkschaefer.bsky.social

Picture this: you are running a single cell sequencing experiment and want to incorporate cells from different species, individuals, and maybe even perturbations. You process everything together to save time while reducing batch artifacts. You collect data. What do you do now?

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Surprisingly, cells with mitochondria from two hominids show evidence for apoptotic pathway induction, reduced mRNA expression, and less efficient processing of polycistronic mitochondrial transcripts, revealing recently evolved incompatibilities in the hominid lineage.

Our analysis revealed that human and bonobo mitochondria typically outcompete those from chimpanzee, but we also identified a fraction of cells where chimpanzee mitochondria win and cells where both mitochondria survive.

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For full details on how the tools work, see: bsky.app/profile/nksc...

Nathan Schaefer@nkschaefer.bsky.social

Picture this: you are running a single cell sequencing experiment and want to incorporate cells from different species, individuals, and maybe even perturbations. You process everything together to save time while reducing batch artifacts. You collect data. What do you do now?

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Importantly, CellBouncer uses sequence variation as an external ground-truth for ambient RNA determination, improving individual-of-origin assignments and enabling cell level corrections, while providing insights into the nature and sources of ambient RNA.

CellBouncer also provides independent validation methods for statistical confidence in assignments, including a tool for determining individual proportion in bulk (and pseudobulk) RNA-seq data

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Pooled processing or culture of cells provides a promising avenue to connect human genetics and single cell genomics but creates new bioinformatic challenges.. CellBouncer provides 7 integrated tools to accelerate pooled experiments, including:

A major goal for our group and the field is to connect naturally occurring genetic variation to cellular phenotypes, across individuals, species, cell types, stimuli, and genetic perturbations.

Alex Pollen reposted

Alex Pollen reposted

By @katherinejwu.com "The NIH... supported 99 percent of the drugs approved in the U.S. from 2010 to 2019. The agency has had a hand in “nearly all of our major medical breakthroughs over the past several decades,” The NIH is in a struggle for its (and our) lives. This is existential to America:

theatlantic.comInside the Collapse at NIHAdministration officials pressured NIH to avoid clear advice from the agency’s own lawyers to restart grant funding now.