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Reconstruction of the mouse otocyst and early neuroblast lineage at single-cell resolution


Durruthy-Durruthy, Robert; Gottlieb, Assaf; Hartman, Byron H; Waldhaus, Jörg; Laske, Roman D; Altman, Russ; Heller, Stefan (2014). Reconstruction of the mouse otocyst and early neuroblast lineage at single-cell resolution. Cell, 157(4):964-978.

Abstract

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.

Abstract

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Otorhinolaryngology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:8 May 2014
Deposited On:09 Feb 2015 14:46
Last Modified:05 Apr 2016 18:49
Publisher:Cell Press (Elsevier)
ISSN:0092-8674
Publisher DOI:https://doi.org/10.1016/j.cell.2014.03.036
PubMed ID:24768691

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