Abstract
Protruding from the apical surface of inner ear sensory cells, hair bundles carry out mechanotransduction. Bundle growth involves sequential and overlapping cellular processes, which are concealed within gene expression profiles of individual cells. To dissect such processes, we developed CellTrails, a tool for uncovering, analyzing, and visualizing single-cell gene-expression dynamics. Utilizing quantitative gene-expression data for key bundle proteins from single cells of the developing chick utricle, we reconstructed de novo a bifurcating trajectory that spanned from progenitor cells to mature striolar and extrastriolar hair cells. Extraction and alignment of developmental trails and association of pseudotime with bundle length measurements linked expression dynamics of individual genes with bundle growth stages. Differential trail analysis revealed high-resolution dynamics of transcripts that control striolar and extrastriolar bundle development, including those that encode proteins that regulate [Ca2+]i or mediate crosslinking and lengthening of actin filaments. Ordering single cells along branching trajectories using transcriptomic data is bioinformatically challenging. Ellwanger et al. developed CellTrails and applied this tool to showcase the bifurcating sequence of gene expression as sensory hair cells develop into different subtypes that feature spatially distinct morphologies of the mechanosensitive hair bundle.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2901-2914.e14 |
| Journal | Cell Reports |
| Volume | 23 |
| Issue number | 10 |
| DOIs | |
| State | Published - Jun 5 2018 |
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Keywords
- clustering
- dimensionality reduction
- dynamic time warping
- hair cell
- inner ear
- software
- spectral embedding
- trajectory reconstruction
- transcriptomics
- vestibular
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Transcriptional Dynamics of Hair-Bundle Morphogenesis Revealed with CellTrails. / Ellwanger, Daniel C.; Scheibinger, Mirko; Dumont, Rachel A.; Barr-Gillespie, Peter; Heller, Stefan.
In: Cell Reports, Vol. 23, No. 10, 05.06.2018, p. 2901-2914.e14.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transcriptional Dynamics of Hair-Bundle Morphogenesis Revealed with CellTrails
AU - Ellwanger, Daniel C.
AU - Scheibinger, Mirko
AU - Dumont, Rachel A.
AU - Barr-Gillespie, Peter
AU - Heller, Stefan
PY - 2018/6/5
Y1 - 2018/6/5
N2 - Protruding from the apical surface of inner ear sensory cells, hair bundles carry out mechanotransduction. Bundle growth involves sequential and overlapping cellular processes, which are concealed within gene expression profiles of individual cells. To dissect such processes, we developed CellTrails, a tool for uncovering, analyzing, and visualizing single-cell gene-expression dynamics. Utilizing quantitative gene-expression data for key bundle proteins from single cells of the developing chick utricle, we reconstructed de novo a bifurcating trajectory that spanned from progenitor cells to mature striolar and extrastriolar hair cells. Extraction and alignment of developmental trails and association of pseudotime with bundle length measurements linked expression dynamics of individual genes with bundle growth stages. Differential trail analysis revealed high-resolution dynamics of transcripts that control striolar and extrastriolar bundle development, including those that encode proteins that regulate [Ca2+]i or mediate crosslinking and lengthening of actin filaments. Ordering single cells along branching trajectories using transcriptomic data is bioinformatically challenging. Ellwanger et al. developed CellTrails and applied this tool to showcase the bifurcating sequence of gene expression as sensory hair cells develop into different subtypes that feature spatially distinct morphologies of the mechanosensitive hair bundle.
AB - Protruding from the apical surface of inner ear sensory cells, hair bundles carry out mechanotransduction. Bundle growth involves sequential and overlapping cellular processes, which are concealed within gene expression profiles of individual cells. To dissect such processes, we developed CellTrails, a tool for uncovering, analyzing, and visualizing single-cell gene-expression dynamics. Utilizing quantitative gene-expression data for key bundle proteins from single cells of the developing chick utricle, we reconstructed de novo a bifurcating trajectory that spanned from progenitor cells to mature striolar and extrastriolar hair cells. Extraction and alignment of developmental trails and association of pseudotime with bundle length measurements linked expression dynamics of individual genes with bundle growth stages. Differential trail analysis revealed high-resolution dynamics of transcripts that control striolar and extrastriolar bundle development, including those that encode proteins that regulate [Ca2+]i or mediate crosslinking and lengthening of actin filaments. Ordering single cells along branching trajectories using transcriptomic data is bioinformatically challenging. Ellwanger et al. developed CellTrails and applied this tool to showcase the bifurcating sequence of gene expression as sensory hair cells develop into different subtypes that feature spatially distinct morphologies of the mechanosensitive hair bundle.
KW - clustering
KW - dimensionality reduction
KW - dynamic time warping
KW - hair cell
KW - inner ear
KW - software
KW - spectral embedding
KW - trajectory reconstruction
KW - transcriptomics
KW - vestibular
UR - http://www.scopus.com/inward/record.url?scp=85047637555&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047637555&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.05.002
DO - 10.1016/j.celrep.2018.05.002
M3 - Article
C2 - 29874578
AN - SCOPUS:85047637555
VL - 23
SP - 2901-2914.e14
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
ER -