Abstract:
:Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties.
journal_name
Cell Repjournal_title
Cell reportsauthors
Poulin JF,Zou J,Drouin-Ouellet J,Kim KY,Cicchetti F,Awatramani RBdoi
10.1016/j.celrep.2014.10.008subject
Has Abstractpub_date
2014-11-06 00:00:00pages
930-43issue
3issn
2211-1247pii
S2211-1247(14)00862-6journal_volume
9pub_type
杂志文章相关文献
Cell Reports文献大全abstract::MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks b...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.031
更新日期:2016-01-12 00:00:00
abstract::The recent success of derivation of mammalian haploid embryonic stem cells (haESCs) has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous dipl...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.07.081
更新日期:2017-08-29 00:00:00
abstract::Development and function of pancreatic β cells involve the regulated activity of specific transcription factors. RFX6 is a transcription factor essential for mouse β cell differentiation that is mutated in monogenic forms of neonatal diabetes. However, the expression and functional roles of RFX6 in human β cells, espe...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.11.010
更新日期:2014-12-24 00:00:00
abstract::The spindle assembly checkpoint (SAC) prevents premature segregation of chromosomes during mitosis. This process requires structural remodeling of MAD2 from O-MAD2 to C-MAD2 conformation. After the checkpoint is satisfied, C-MAD2 is reverted to O-MAD2 to allow anaphase-promoting complex/cyclosome (APC/C) to trigger an...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.01.027
更新日期:2018-02-06 00:00:00
abstract::Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knoc...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.01.063
更新日期:2018-02-13 00:00:00
abstract::Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.11.012
更新日期:2017-11-28 00:00:00
abstract::The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance e...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.09.022
更新日期:2017-10-03 00:00:00
abstract::Here, we propose an approach to identify active metabolic pathways by integrating gene essentiality analysis and protein abundance. We use two bacterial species (Mycoplasma pneumoniae and Mycoplasma agalactiae) that share a high gene content similarity yet show significant metabolic differences. First, we build detail...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107722
更新日期:2020-06-02 00:00:00
abstract::Successful anti-viral response requires the sustained activation and expansion of CD8+ T cells for periods that far exceed the time limit of physical T cell interaction with antigen-presenting cells (APCs). The expanding CD8+ T cell pool generates the effector and memory cell populations that provide viral clearance a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.075
更新日期:2018-07-31 00:00:00
abstract::HIV-1 uses the microtubule network to traffic the viral capsid core toward the nucleus. Viral nuclear trafficking and infectivity require the kinesin-1 adaptor protein FEZ1. Here, we demonstrate that FEZ1 directly interacts with the HIV-1 capsid and specifically binds capsid protein (CA) hexamers. FEZ1 contains multip...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.07.079
更新日期:2019-08-27 00:00:00
abstract::Chronic exposure to nicotine upregulates nicotinic acetylcholine receptors (nAChRs), and such upregulation is critical for the development of nicotine dependence in humans and animal models. However, how nicotine upregulates nAChRs is not well understood. Here, we identify a key role for microRNA in regulating nicotin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.043
更新日期:2017-11-07 00:00:00
abstract::Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.044
更新日期:2019-03-12 00:00:00
abstract::Whole-body regeneration relies on the re-establishment of body axes for patterning of new tissue. Wnt signaling is required to correctly regenerate tissues along the primary axis in many animals. However, the causal mechanisms that first launch Wnt signaling during regeneration are poorly characterized. We use the aco...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108098
更新日期:2020-09-01 00:00:00
abstract::Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107881
更新日期:2020-07-14 00:00:00
abstract::Although it is well established that tumor-associated macrophages take part in each step of cancer progression, less is known about the distinct role of the so-called metastasis-associated macrophages (MAMs) at the metastatic site. Previous studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor-sup...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.11.034
更新日期:2017-12-05 00:00:00
abstract::Lineage analysis of autoreactive B cells can reveal the origins of autoimmunity. In the autoimmune disease pemphigus vulgaris (PV), desmoglein 3 (DSG3) and DSG1 autoantibodies are predominantly of the IgG4 subclass and less frequently of IgG1 and IgA subclasses, prompting us to investigate whether anti-DSG IgG4 B cell...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.07.093
更新日期:2018-08-28 00:00:00
abstract::Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor γ (PPARγ) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicot...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.10.018
更新日期:2012-12-27 00:00:00
abstract::The local synthesis of transmembrane proteins underlies functional specialization of dendritic microdomains in neuronal plasticity. It is unclear whether these proteins have access to the complete machinery of the secretory pathway following local synthesis. In this study, we describe a probe called pGolt that allows ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.12.024
更新日期:2016-01-12 00:00:00
abstract::The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extend...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.060
更新日期:2018-01-09 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) is a transcription factor central to axon regrowth with an enigmatic ability to act in different subcellular regions independently of its transcriptional roles. However, its roles in mature CNS neurons remain unclear. Here, we show that along with nuclear tran...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.03.029
更新日期:2016-04-12 00:00:00
abstract::Chromatin interactions play important roles in transcription regulation. To better understand the underlying evolutionary and functional constraints of these interactions, we implemented a systems approach to examine RNA polymerase-II-associated chromatin interactions in human cells. We found that 40% of the total gen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.09.022
更新日期:2012-11-29 00:00:00
abstract::A mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) typically expresses one allele of one odorant receptor (OR) gene. It is widely thought that the great majority of the 1,141 intact mouse OR genes are expressed in one of four MOE zones (or bands or stripes), which are largely non-overlappin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.110
更新日期:2020-03-24 00:00:00
abstract::Dentate gyrus (DG) development requires specification of granule cell (GC) progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.044
更新日期:2018-01-09 00:00:00
abstract::In the presynaptic terminal, the magnitude and location of Ca2+ entry through voltage-gated Ca2+ channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.024
更新日期:2018-07-10 00:00:00
abstract::In the absence of low-level ER-to-mitochondrial Ca(2+) transfer, ATP levels fall, and AMPK-dependent, mTOR-independent autophagy is induced as an essential survival mechanism in many cell types. Here, we demonstrate that tumorigenic cancer cell lines, transformed primary human fibroblasts, and tumors in vivo respond s...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.02.030
更新日期:2016-03-15 00:00:00
abstract::T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell developme...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.01.015
更新日期:2016-02-16 00:00:00
abstract::Nucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-tran...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.02.038
更新日期:2015-03-17 00:00:00
abstract::Most tumor cells exhibit obligatory demands for essential amino acids (EAAs), but the regulatory mechanisms whereby tumor cells take up EAAs and EAAs promote malignant transformation remain to be determined. Here, we show that oncogenic MYC, solute carrier family (SLC) 7 member 5 (SLC7A5), and SLC43A1 constitute a fee...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.002
更新日期:2017-12-26 00:00:00
abstract::Chromodomain Helicase DNA binding protein 5 (CHD5) is a tumor suppressor mapping to 1p36, a genomic region that is frequently deleted in human cancer. Although CHD5 belongs to the CHD family of chromatin-remodeling proteins, whether its tumor-suppressive role involves an interaction with chromatin is unknown. Here we ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.12.009
更新日期:2013-01-31 00:00:00
abstract::Pathogens trigger T cells to express distinct sets of effector proteins. To better understand the molecular mechanisms that drive functional specification, we used high-resolution mass spectrometry and label-free protein quantification to measure proteomic differences between the seven largest circulating human CD8+ T...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.04.014
更新日期:2017-05-02 00:00:00