Thanks to all of our lab members and collaborators @nanamatoba.bsky.social @steinlab.bsky.social @mikegandal.bsky.social and Geschwind lab for their important contributions to this work.
07.07.2025 20:58 — 👍 0 🔁 0 💬 0 📌 0
A single cell multi-omic analysis identifies molecular and gene-regulatory mechanisms dysregulated in the developing Down syndrome neocortex
Down syndrome is the most common genetic cause of intellectual disability, presenting with cognitive, learning, memory, and language deficits. The cellular and molecular mechanisms driving this disorder remain unclear, limited by a lack of systematic studies in the developing human brain. Here, we leveraged single-nucleus multi-omics to profile the mid-gestation neocortex in a cohort of 26 donors. We observed a reduction in neural progenitors and corticothalamic neurons and concomitant increase of intratelencephalic neurons, accompanied by accelerated time to neuronal specification. We uncovered widespread changes in gene expression, chromatin accessibility and cell interaction networks impacting neurogenesis, specification and maturation and gene-regulatory networks directing these processes, including those downstream of transcription factors encoded in chromosome 21. Finally, we identified cell-specific molecular pathways shared with other neurodevelopmental disorders as well as heritability enrichment of GWAS signals in altered chromatin. Together, our data revealed a cascade of molecular dysregulation outlining the earliest steps in Down syndrome, providing a foundation for future therapeutic targets. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, R21HD108606, R01MH124018, T32LM012424 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Rose Hills Foundation Innovator Grant, Postdoctoral Training Program, Ablon Scholars Program
New preprint from our lab led by an amazing team,
Celine Vuong and Alexis Weber, where we employ single-cell multi-omics in the developing brain to uncover mechanisms of Down syndrome.
#brain #singlecell #multiomics #DownSyndrome
www.biorxiv.org/content/10.1...
07.07.2025 20:54 — 👍 3 🔁 0 💬 1 📌 0
Stem cell scientist in a genomics world🧬🧠. Mom to a third-grader! 🌈🦄. Wife. Runner🏃♀️🚴♀️🏂. Immigrant 🇨🇦. @MountSinaiNYC to @YaleMed. she/her.
Developmental neurobiologist and human organoids aficionado. Associate Prof. @USCStemCell. Director @USC CIRM ASCEND Shared Resource Lab. Mama^2. Immigrant 🇮🇹.
https://quadratolab.usc.edu/
https://ascend.usc.edu/
Group Leader at Helmholtz Center Munich * Brain Epigenomics
UCSD and Rady Genomics Institute Lab. CMO of n-Lorem Foundation, studying pediatric brain disease.
developmental neurobiologist, child neurologist
Lab: Sahin-lab.org
Neuroscientist & geneticist studying neurodev, autism, and DDX3X | PREP Director | Immigrant | 2x mom | #firstgen | #Humboldtian (she/her)
Born and raised in 🇮🇹, had fun in 🇧🇪, transplanted in 🇺🇸
Views my own
https://labs.icahn.mssm.edu/derubeislab/
Neuroscientist and Assistant Professor at UCLA | SFARI BTI Fellow | Psychiatric genetics and neuroimaging
UCLA Professor (Neuroscience/Psychology) & dog/human mama 💙💛 *views expressed r entirely my own*
Developmental neurobiologist using cerebral #organoids to study brain size and evolution. Opinions my own.
Developing methods & assembling data to explore multi-omic dynamics across cell contexts, in stem cell models & neocortical development, neurodegeneration and neuroinflammation in particular: http://carlocolantuoni.org
Assistant Professor @ UCLA Pathology, Computational Medicine, Biostatistics, and Genetics
Developmental Neurobiology | Autism | Epilepsy | Cortex | Neural stem cells | mouse | human
Assistant Professor Weill Cornell Medicine.
UCLA, University of Sheffield, University of Newcastle upon Tyne alum
capearsonlab.com
(Posts my own opinions)
Scientist, prof at Duke, mom, food, travel, ocean lover. Fascinated by how the brain develops and is modified in disease and evolution. RNA biology intersects neural development. Views my own not employer. https://sites.duke.edu/silverlab/
Cell Press partners with scientists across all disciplines to publish and share work that will inspire future directions in research. #ScienceThatInspires
Associate of Professors, Aficionado of Synapses, Runner of Miles, Practicer of Kindness, Tracker of Tenure, Denizen of South Philly. My thoughts are mine. He/his/him. Signal: drosophilosophy.07 (you know, if you ever need to talk). www.moscalab.org
Assistant prof at UCLA using the Bayes for the genomes https://pimentellab.com
Understanding life. Advancing health.
Epigenetics & Genomics
Harvard University & Broad Institute
https://www.macfound.org/fellows/class-of-2023/jason-d-buenrostro
buenrostrolab.com
Posting our lab life studying the neuronal cytoskeleton and chromatin with cool microscopes🔬Proud #GenX, #firstgen college, #intj @RITscience @stonybrooku Alum
Verified: https://orcid.org/0000-0001-8481-0403
