Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell-Surface Proteomic Profiling in the Fly Brain Uncovers New Wiring Regulators

ABSTRACT: Li J, Han S, Li H, Udeshi ND, Svinkina T, Mani DR, Xu C, Guajardo R, Xie Q, Li T, Luginbuhl DJ, Wu B, McLaughlin CN, Xie A, Kaewsapsak P, Quake sR, Carr SA, Ting AY, Luo L. 2019. Molecular interactions at the cellular interface mediate organized assembly of single cells into tissues, and thus govern the development and physiology of multicellular organisms. Here, we developed a cell-type-specific, spatiotemporally-resolved approach to profile cell-surface proteomes in intact tissues. Quantitative profiling of cell-surface proteomes of Drosophila olfactory projection neurons (PNs) in pupae and adults revealed a global down-regulation of wiring molecules and an up-regulation of synaptic molecules in the transition from developing to mature PNs. A proteome-instructed in vivo screen identified 20 new cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. Genetic analysis further revealed that the lipoprotein receptor LRP1 cell-autonomously controls PN dendrite targeting, contributing to the formation of a precise olfactory map. These findings highlight the power of temporally-resolved in situ cell-surface proteomic profiling in discovering new regulators of brain wiring.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Drosophila <fruit Fly, Genus> (ncbitaxon:7215)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000084543 | MassIVE | Wed Nov 06 06:40:00 GMT 2019

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptomic analysis of Drosophila olfactory projection neurons

Project description:Molecular interactions at the cellular interface mediate organized assembly of single cells into tissues, and thus govern the development and physiology of multicellular organisms. Here, we developed a cell-type-specific, spatiotemporally-resolved approach to profile cell surface proteomes in intact tissues. Quantitative profiling of cell-surface proteomes of Drosophila olfactory projection neurons (PNs) in pupae and adults revealed a global downregulation of wiring molecules and an up-regulation of synaptic molecules in the transition from developing to mature PNs. To compare the RNA and protein dynamics of PN surface molecules in the developing-to-mature transition, we also profiled the PN transcriptomes from 36hAPF pupae and 5d adults. We performed bulk RNA-sequencing of PNs with 3 samples for each stage and 2k cells for each sample.

2019-12-19 | GSE140093 | GEO

Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-cell RNA Sequencing

Project description:How a neuronal cell type is defined and how this relates to its transcriptome are still open questions. The Drosophila olfactory projection neurons (PNs) are among the bestcharacterized neuronal types: Different PN classes target dendrites to distinct olfactory glomeruli and PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA-sequencing, we comprehensively characterized the transcriptomes of 40 PN classes and unequivocally identified transcriptomes for 6 classes. We found a new lineage-specific transcription factor that instructs PN dendrite targeting. Transcriptomes of closely-related PN classes exhibit the largest difference during circuit assembly, but become indistinguishable in adults, suggesting that neuronal subtype diversity peaks during development. Genes encoding transcription factors and cell-surface molecules are the most differentially expressed, indicating their central roles in specifying neuronal identity. Finally, we show that PNs use highly redundant combinatorial molecular codes to distinguish subtypes, enabling robust specification of cell identity and circuit assembly.

2017-10-21 | GSE100058 | GEO

Transcription Factor Acj6 Specifies Distinct Dendrite Targets via Unique Cell-Surface Protein Combinations

Project description:Xie Q, Li J1, Li H, Udeshi ND, Svinkina T, Kohani S, Guajardo R, Mani DR, Xu C, Li T, Han S, Wei W, Shuster SA, Luginbuhl DJ, Ting AY, Carr SA, Luo L. 2022. Transcription factors specify the fate and connectivity of developing neurons. To understand how distal neurites execute commands from these nucleus-residing factors to specify their connectivity, we investigated how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs). Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and molecules previously not associated with wiring, such as the mechanosensitive ion channel Piezo. Ion channel activity is dispensable for Piezo's function in PN dendrite targeting. Combinatorial expression of Acj6 executors more strongly rescued specific acj6 mutant phenotypes than expression of individual executors. Together, our findings reveal that a key transcription factor controls wiring specificity of different neuron types by regulating expression of unique combinations of cell-surface executors.

2022-04-01 | MSV000089187 | MassIVE

Up regulation of lactosamine containing glycans

2011-03-02 | E-GEOD-27590 | biostudies-arrayexpress

The human nose harbours a niche of olfactory ecto-mesenchymal stem cells displaying neurogenic and osteogenic properties

Project description:We previously identified multipotent stem cells within the lamina propria of the human olfactory mucosa, located in the nasal cavity. We also demonstrated that this cell type differentiates into neural cells and improves locomotor behavior after transplantation in a rat model of Parkinsonâs disease. Yet, next to nothing is known about their specific stemness characteristics. We therefore devised a study aiming to compare olfactory lamina propria stem cells from 4 individuals to bone marrow mesenchymal stem cells from 4 age- and gendermatched individuals. Using pangenomic microarrays and immunostaining with 34 cell surface marker antibodies, we show here that olfactory stem cells are closely related to bone marrow stem cells. However, olfactory stem cells exhibit also singular traits. By means of techniques such as proliferation assay, cDNA microarrays, RT-PCR, in vitro and in vivo differentiation, we report that, when compared to bone marrow stem cells, olfactory stem cells display i) a high proliferation rate; ii) a propensity to differentiate into osseous cells and iii) a disinclination to give rise to chondrocytes and adipocytes. Since peripheral olfactory stem cells originate from a neural crest-derived tissue and, as shown here, exhibit an increased expression of neural cellrelated genes, we propose to name them olfactory ecto-mesenchymal stem cells (OE-MSC). Further studies are now required to corroborate the therapeutic potential of OE-MSCs in animal models of bone and brain diseases. Keywords: cell type comparison Expression profiles of olfactory ectomesenchymal stem cells, bone marrow MSC, periosteal cells, neural progenitors, and synovial fibroblasts were compared against each other and with different lineages of purified hematopoietic cells from bone marrow to characterise human olfactory ectomesenchymal stem cells molecularly

2010-10-08 | E-GEOD-24598 | biostudies-arrayexpress

In situ cell-surface proteomic profiling in mice

Project description:Shuster SA, Li J, Chon U, Hu MC, Luginbuhl DJ, Udeshi ND, Carey DK, Takeo YH, Xu C, Mani D.R., Han S, Ting AY, Carr SA, Luo L. Cell-surface proteins mediate cell-cell interactions throughout the lifetime of multicellular organisms, yet there are no general methods for profiling them in vertebrate tissues. Here, we present in-situ cell-surface proteome extraction by extracellular labeling (iPEEL) in mice, which enables cell-type-specific profiling of cell-surface proteomes in native tissues. Applying iPEEL to developing and mature cerebellar Purkinje cells revealed a differential enrichment in cell-surface proteins with post-translational processing and synaptic functions in the developing and mature proteomes, respectively. A proteome-instructed in vivo loss-of-function screen identified a critical role for Armadillo-like helical domain-containing protein 4 (Armh4) in Purkinje cell dendrite morphogenesis. Armh4 overexpression also disrupts dendrite morphogenesis; this effect requires its conserved cytoplasmic domain and is augmented by disruption of endocytosis. Our results highlight the utility of cell-surface proteomic profiling in native tissues in identifying regulators of cell-surface signaling events.

2021-12-03 | MSV000088506 | MassIVE

Up regulation of lactosamine containing glycans

2011-03-02 | GSE27590 | GEO

The human nose harbours a niche of olfactory ecto-mesenchymal stem cells displaying neurogenic and osteogenic properties

Project description:We previously identified multipotent stem cells within the lamina propria of the human olfactory mucosa, located in the nasal cavity. We also demonstrated that this cell type differentiates into neural cells and improves locomotor behavior after transplantation in a rat model of Parkinson’s disease. Yet, next to nothing is known about their specific stemness characteristics. We therefore devised a study aiming to compare olfactory lamina propria stem cells from 4 individuals to bone marrow mesenchymal stem cells from 4 age- and gendermatched individuals. Using pangenomic microarrays and immunostaining with 34 cell surface marker antibodies, we show here that olfactory stem cells are closely related to bone marrow stem cells. However, olfactory stem cells exhibit also singular traits. By means of techniques such as proliferation assay, cDNA microarrays, RT-PCR, in vitro and in vivo differentiation, we report that, when compared to bone marrow stem cells, olfactory stem cells display i) a high proliferation rate; ii) a propensity to differentiate into osseous cells and iii) a disinclination to give rise to chondrocytes and adipocytes. Since peripheral olfactory stem cells originate from a neural crest-derived tissue and, as shown here, exhibit an increased expression of neural cellrelated genes, we propose to name them olfactory ecto-mesenchymal stem cells (OE-MSC). Further studies are now required to corroborate the therapeutic potential of OE-MSCs in animal models of bone and brain diseases. Keywords: cell type comparison

2010-10-08 | GSE24598 | GEO

Microarray screening of RNA samples from the olfactory epithelium from wild type and beta3GnT1 mutant mice

Project description:Dr. Schwarting's research is focused on the analysis of developmentally regulated cell surface molecules and their role in axon guidance and neuronal migration, using the olfactory system as a model. The interaction of cell surface glycans with endogenous lectins in the extracellular matrix provides one mechanism by which axons can utilize specific pathways as they grow towards their targets. Beta3GnT1 mutant mice lose lactosamine expression and have an olfactory axon guidance phenotype (Henion et al, 2005). Olfactory neurons are capable of regeneration and we know that when these neurons regenerate in beta3GnT1 mutant they synthesize lactosamine by a secondary mechanism. By comparing RNA from the olfactory epithelium from wild type and mutant mice, we would expect to see the upregulation of glycosyltransferases that could produce lactosamine in the absence of beta3GnT1. In a preliminary experiment carried out by the CFG staff, we saw that radical fringe, a beta 3GnT, was upregulated in the olfactory epithelium, although it is probably not responsible for the new lactosamine expression. beta3GnT1 Knock out. Strain info: The b3GnT1 mice were generated on a mixed 129Ola-C57BL/6 background and backcrossed to C57BL/6 for four generations. They were then crossed to I7-Internal ribosomal entry site (IRES)-tau greeen fluorescent protein (GFP) mice generated by Dr. Peter Mombaerts.

2011-04-29 | GSE28926 | GEO

Microarray screening of RNA samples from the olfactory epithelium from wild type and beta3GnT1 mutant mice

2011-04-29 | E-GEOD-28926 | biostudies-arrayexpress