Reconstruction of the Mouse Otocyst and Early Neuroblast Lineage at Single-Cell Resolution
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The otocyst harbors progenitors for most cell types of the mature inner ear. Developmental lineage analyses and gene expression studies suggest that distinct progenitor populations are compartmentalized to discrete axial domains in the early otocyst. Here, we conducted highly parallel quantitative RT-PCR measurements on 382 individual cells from the developing otocyst and neuroblast lineages to assay 96 genes representing established otic markers, signaling-pathway-associated transcripts, and novel otic-specific genes. By applying multivariate cluster, principal component, and network analyses to the data matrix, we were able to readily distinguish the delaminating neuroblasts and to describe progressive states of gene expression in this population at single-cell resolution. It further established a three-dimensional model of the otocyst in which each individual cell can be precisely mapped into spatial expression domains. Our bioinformatic modeling revealed spatial dynamics of different signaling pathways active during early neuroblast development and prosensory domain specification.
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scRNA-seq makes it possible to study the mechanisms underlying allele-intrinsic variation by examining differences in other moments of the distribution (e.g., variance), which can shed light on the kinetics of the transcription process.
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Self-citation
- Authors
- Durruthy-Durruthy, R., Gottlieb, A., Hartman, B. H., Waldhaus, J., Laske, R. D., Altman, R., & Heller, S.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Heller, Stefan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 157
- Issue
- 4
- Pages
- 964-978
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4051200
- OpenAlex
- W2000348340
- Cited by
- 148
- References
- 64
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 13 · 2021: 13 · 2020: 14 · 2019: 10 · 2018: 10 · 2017: 14 · 2016: 13 · 2015: 31 · 2014: 6
- FWCI
- 13.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- European Commission
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders (R01DC006167, P30DC010363, DC012250, DC006167, R01DC004563, R01DC012250, F32DC013210)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- otocyst, neuroblast lineage, inner ear development, single-cell gene expression, delamination, signaling pathways, mouse embryo
- MeSH terms
- Animals, Embryo, Mammalian, Female, Ear, Inner, Male, Gene Expression Regulation, Developmental, Principal Component Analysis, Mice, Neural Stem Cells, Single-Cell Analysis, Transcriptome
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