Dissecting Cell-Type Composition and Activity-Dependent Transcriptional State in Mammalian Brains by Massively Parallel Single-Nucleus RNA-Seq
Open accessPublished version of a preprint
Abstract
Massively parallel single-cell RNA sequencing can precisely resolve cellular diversity in a high-throughput manner at low cost, but unbiased isolation of intact single cells from complex tissues such as adult mammalian brains is challenging. Here, we integrate sucrose-gradient-assisted purification of nuclei with droplet microfluidics to develop a highly scalable single-nucleus RNA-seq approach (sNucDrop-seq), which is free of enzymatic dissociation and nucleus sorting. By profiling ∼18,000 nuclei isolated from cortical tissues of adult mice, we demonstrate that sNucDrop-seq not only accurately reveals neuronal and non-neuronal subtype composition with high sensitivity but also enables in-depth analysis of transient transcriptional states driven by neuronal activity, at single-cell resolution, in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 36 · Cited by 162
- Authors
- Hu, P., Fabyanic, E., Kwon, D. Y., Tang, S., Zhou, Z., & Wu, H.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Wu, Hao
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 68
- Issue
- 5
- Pages
- 1006-1015.e7
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5743496
- OpenAlex
- W2775417722
- Cited by
- 162
- References
- 36
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 21 · 2023: 25 · 2022: 24 · 2021: 21 · 2020: 19 · 2019: 17 · 2018: 14 · 2017: 1
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (R00HG007982)
- National Heart Lung and Blood Institute (DP2HL142044)
- Penn Epigenetics Institute
- National Institute of Mental Health (R56MH111719)
- T32 Training Program in Cell and Molecular Biology (T32-GM007229)
- T32 Training Program in Neurodevelopmental Disabilities (T32-NS007413)
- NRAS (F3, 0, -NS100433)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- single-nucleus RNA sequencing, droplet microfluidics, neuronal cell types, cortical transcriptome, activity-dependent transcription, neuronal activity, mouse brain
- MeSH terms
- Human Embryonic Stem Cells, Animals, Cell Nucleus, Centrifugation, Density Gradient, Cerebral Cortex, Disease Models, Animal, Humans, Kinetics, Male, Mice, Inbred C57BL, Neural Inhibition, Synaptic Transmission, Neurons, Pentylenetetrazole, RNA, Seizures, Transcription, Genetic, Transfection, Sequence Analysis, RNA, NIH 3T3 Cells, Microfluidic Analytical Techniques, Mice, Single-Cell Analysis, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
