Alex Pollen

Grateful for @enardhellmannwg.bsky.social labs to host @nkschaefer.bsky.social and exchange ideas about village cell culture and human-specific evolution with experts at LMU Munich, including the Hellman and Enard labs as well as @boyanbonev.bsky.social!

We’re excited to host @nkschaefer.bsky.social from the Pollen Lab @brainevodevo.bsky.social, UCSF!
He’ll present Cellbouncer, a new bioinformatic tool for pooled single-cell processing that yields insights into hominid evolution 🧬

More about the lab 👉 www.pollenlab.org

Trump preparing large-scale cancellation of federal funding for California, sources say | CNN Politics The 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.

"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.

Developmental timing across species: From mechanisms to evolutionary insights Like choreography, development consists of a highly ordered suite of steps and transitions. Modifying developmental tempo can affect final size and composition of tissues, as well as their plasticity…

EMBOMtg Paris May 6-9
@aydoganlab.bsky.social @jamesbriscoe.bsky.social @brunetlab.bsky.social @ebisuyamiki.bsky.social @mwdorr.bsky.social @beyerlab.bsky.social @franckp.bsky.social @janereznick.bsky.social @olmedo-lab.bsky.social @perez-carrasco.bsky.social
meetings.embo.org/event/25-dev...

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

We hope that CellBouncer will accelerate population-scale single cell genomic analyses, improve ambient RNA correction, and enable new experimental designs not previously possible.

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.

We put CellBouncer to the test with a challenging demultiplexing problem of assigning 24 hominid tetraploid composite cell lines generated by Bryan Pavlovic to both individuals-of-origin and identifying the mitochondrial haplotypes present.

www.biorxiv.org/content/10.1...

CellBouncer tools were crucial for our study of dopaminergic evolution that included ventral midbrain organoids with up to 17 individuals from 4 species, led by Sara Nolbrant, @jenellewallace.bsky.social, and Jingwen Ding:
www.biorxiv.org/content/10.1...

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

Finally, CellBouncer harmonizes independent metrics for doublet identification to produce a global doublet rate

CellBouncer assigns sgRNAs and other perturbation tags to cell-of-origin, accounting for low coverage and increased tag background

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

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.

Genotype-free assignments for an unknown number of individuals by discovery of mitochondrial haplotypes

Individual-of-origin assignments for cells that account for deep population structure, scale across large SNP sets, and are robust to ambient RNA

Alignment-free rapid species assignments with an underlying statistical model

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.

Introducing CellBouncer, a unified demultiplexing toolkit built by nkschaefer.bsky.social to check IDs and keep the riff raff out of single cell genomics datasets, including by using genetic variation as an external ground-truth for ambient RNA removal:

www.biorxiv.org/content/10.1...

Metabolic Atlas of Early Human Cortex Identifies Regulators of Cell Fate Transitions Characterization of cell type emergence during human cortical development, which enables unique human cognition, has focused primarily on anatomical and transcriptional characterizations. Metabolic pr...

Excellent preprint by @bhadurilab.bsky.social, offering a metabolic atlas of the early human cortex, & revealing how shifts in metabolic processes regulate cell fate transitions. Very valuable resource to address evolutionary questions 🧪🧠🧫
www.biorxiv.org/content/10.1...

Francis Collins, the NIH Director for 12 years, led the Human Genome Project and other NIH efforts for 32 years, resigned today. Key words from his resignation letter
www.nytimes.com/2025/03/01/u...

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

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:

Check out our new preprint describing CiFi - a method that couples 3C and PacBio HiFi sequencing with low input requirements. We apply it to human GM12878 to better characterize chromatin across repetitive regions, as well as single insect samples (a mosquito and a Mediterranean fruit fly).

and @vanderhaeghenp2.bsky.social derhaeghenp2.bsky.social, @psudmant.bsky.social sudmant.bsky.social , Genevieve Konopka, Andre Sousa, Genevieve Housman, Ewoud Schmidt, Steve Reilly, @cecilecharrier.bsky.social rrier.bsky.social, @noonanlab.bsky.social y.social, Michael Heide

Congrats to the many authors, including @gtestaccount.bsky.social, @cedricboeckx.bsky.social, Tony Capra, Craig Lowe, Josh Akey, @franckp.bsky.social, @thesilverlab.bsky.social, @blibep.bsky.social...

Pleasure to co-edit this issue of Current Opinion on human genetic origins with @steinlab.bsky.social:

www.sciencedirect.com/special-issu...

Super Enzyme Regulates Testosterone Levels In Male Ruffs A single gene in the shorebird species known as ruffs controls the levels of testosterone in males, and this in turn affects their appearance and mating strategies.

A new story about our recent paper came out today in the Science section of Forbes! Check it out! www.forbes.com/sites/grrlsc...

Day 50 cortical organoid stained for KI67 (red), MAP2 (magenta), Hoechst (cyan); image credit: Oliviero Leonardi

DIV 28 iNeuron. Homer1 in green and Synapsin1 in purple showing co-localization of post- and pre-synapses, respectively; image credit: Elly Lewerissa

New preprint 📣! Excited to share the result of several years of work, led by @ellylewerissa.bsky.social & @olivieroleonardi.bsky.social, in collaboration with friends @naelnadifkasri-lab.bsky.social & Giuseppe Testa. On CHD2, a chromatin remodeller, its role in evolution & development [🧵]
🧪🧠🧫🧬