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GSE108404
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The mechanisms instructing genesis of neuronal subtypes from mammalian neural precursors are not well-understood. To address this issue, we have characterized the transcriptional landscape of radial glial precursors (RPs) in the embryonic murine cortex. We show that individual RPs express mRNA but not protein for transcriptional specifiers of both deep and superficial layer cortical neurons. Some of these mRNAs, including the superficial versus deep layer neuron transcriptional regulators Brn1 and Tle4, are translationally repressed by their association with the RNA-binding protein Pumilio2 and the 4E-T protein. When these repressive complexes are disrupted in RPs mid-neurogenesis by knocking down 4E-T or Pum2, this causes aberrant co-expression of deep layer neuron specification proteins in newborn superficial neurons. Thus, cortical RPs are transcriptionally primed to generate diverse types of neurons, and a 4E-T-Pum2 complex represses translation of some of these neuronal identity mRNAs to ensure appropriate temporal specification of daughter neurons.
Publication Title
A Translational Repression Complex in Developing Mammalian Neural Stem Cells that Regulates Neuronal Specification.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
NextSeq 500
Description
Adult neural stem cells (NSCs) derive from embryonic precursors, but little is known about how or when this occurs. We have addressed this issue using single cell RNAseq at multiple developmental timepoints to analyze the embryonic murine cortex, one source of adult forebrain NSCs. We computationally identify all major cortical cell types, including the embryonic radial precursors (RPs) that generate adult NSCs. We define the initial emergence of RPs from neuroepithelial stem cells at E11.5. We show that by E13.5 these RPs express a transcriptional identity that is maintained and reinforced throughout their transition to a non-proliferative state between E15.5 and E17.5. These slowly-proliferating late embryonic RPs share a core transcriptional phenotype with quiescent adult forebrain NSCs. Together, these findings support a model where cortical RPs maintain a core transcriptional identity from embryogenesis through to adulthood, and where the transition to a quiescent adult NSC occurs during late neurogenesis. Overall design: We applied the high-throughput single-cell mRNA sequencing technique, Drop-seq, to the embryonic mouse cortex. 2000-5000 single cells from wildtype CD1 embryos of gestational ages E11.5, E13.5, E15.5 and E17.5 were characterized.
Publication Title
Developmental Emergence of Adult Neural Stem Cells as Revealed by Single-Cell Transcriptional Profiling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 26 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
Publication Title
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The neural stem cell decision to self-renew or differentiate is tightly regulated by its microenvironment. Here, we have asked about this microenvironment, focusing on growth factors in the embryonic cortex at a time when it is largely comprised of neural precursor cells (NPCs) and newborn neurons. We show that cortical NPCs secrete factors that promote their maintenance while cortical neurons secrete factors that promote differentiation. To define factors important for these activities, we used transcriptome profiling to identify ligands produced by NPCs and neurons, cell surface mass spectrometry to identify receptors on these cells, and computational modeling to integrate these data. The resultant model predicts a complex growth factor environment with multiple autocrine and paracrine interactions. We tested this communication model, focusing on neurogenesis, and identified IFN, Nrtn and glial-derived neurotrophic factor (GDNF) as ligands with unexpected roles in promoting neurogenic differentiation of NPCs in vivo.
Publication Title
Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
Publication Title
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
Publication Title
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair.
Sample Metadata Fields
Treatment
View Samples- Mus musculus, Rattus norvegicus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dedifferentiated Schwann Cell Precursors Secreting Paracrine Factors Are Required for Regeneration of the Mammalian Digit Tip.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on SKPs (skin-derived precursors) a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated 5 such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKPs self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy.
Publication Title
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair.
Sample Metadata Fields
Treatment
View Samples