Transcriptomic characterization of preoptic area in homeostatic sleep controls using single-nucleus RNA-sequencing
使用单核 RNA 测序对稳态睡眠控制中视前区的转录组学特征
基本信息
- 批准号:10373184
- 负责人:
- 金额:$ 44.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-29 至 2024-03-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenosineAffectAnatomyArousalAstrocytesCell NucleusCellsCoupledDataDiseaseDissectionEquilibriumFOS geneFluorescent in Situ HybridizationFreezingFutureGalaninGene ExpressionGene set enrichment analysisGenesGenetic TranscriptionHealthHomeostasisHypothalamic structureIn Situ HybridizationIndividualKnock-outMaintenanceMammalsMapsMolecularMusNeurogliaNeuronsNeuropeptidesPatternPlayPreoptic AreasPropertyRecoveryRoleSignal TransductionSleepSleep DeprivationSleep DisordersSleep Disorders TherapySpecificitySystemTechniquesTimeTissuesTranscriptional RegulationWakefulnessZebrafishage relatedbasebrain cellbrain tissuecell typedifferential expressionhigh rewardhigh riskinhibitory neuronmolecular markernervous system disordernon rapid eye movementnovel therapeuticspreoptic nucleuspressureresponsesingle-cell RNA sequencingsleep regulationtranscriptome sequencingtranscriptomics
项目摘要
ABSTRACT
Sleep homeostasis maintains the balance between sleep and wakefulness. Homeostatic sleep regulation is
essential for cellular health and sleep disorders are implicated in many neurological disorders and age-related
diseases. Understanding sleep homeostatic mechanisms is necessary for developing new therapies for sleep
disorders. The preoptic area (POA) of the hypothalamus is essential for sleep homeostasis. Multiple nuclei of
POA, including the ventrolateral preoptic area (VLPO) and the median preoptic nucleus (MnPO), contain sleep-
active neurons that display increased activity during sleep compared with wake. The numbers of c-Fos positive
neurons in VLPO and MnPO increase under high sleep pressure, e.g. after sleep deprivation and during recovery
sleep following sleep deprivation. The complete makeup of the sleep-active neurons in POA is unknown. The
galanin-expressing GABAergic neurons in VLPO are the most widely studied sleep-active neurons. However,
not all c-Fos positive sleep-active neurons express galanin and not all galanin neurons are c-Fos positive during
sleep at any given time in POA. Given the heterogeneous molecular and functional makeup of POA, it is
important to comprehensively characterize the sleep-active neurons in POA at the individual cell level in an
unbiased way. Towards this end, we will apply the recently advanced single-nucleus RNA sequencing (snRNA-
seq) technique to POA and compare gene expression changes in individual cells between mice during recovery
sleep following sleep deprivation (high sleep pressure) and mice after long periods of spontaneous sleep (low
sleep pressure). Aim 1 will comprehensively map all neuronal groups that are activated under high sleep
pressure based on a panel of activity-regulated genes. We expect to find that specific subtypes of galanin-
expressing inhibitory neurons, as well as non-galanin expressing inhibitory neuronal groups that express other
neuronal markers, are activated with high sleep pressure. Aim 2 will reveal the transcriptional changes regulated
by homeostatic sleep pressure in all cell groups, including neurons and non-neuronal cells. For example,
astrocytes play key roles in maintenance of sleep homeostasis. However, little is known about transcriptional
regulation of astrocytes involved in sleep homeostasis in POA. Given the recent discovery of the molecular and
regional specificity of astrocytes, we hypothesize that we will reveal region-specific and cell-specific changes in
astrocytes. Aim 3 will use multiplex fluorescent in situ hybridization (RNAscope) to characterize the anatomical
localization of the identified sleep-active neurons based on the molecular markers identified by snRNA-seq. This
combination of molecular and spatial characterization of the sleep-active neurons in POA will enable future
dissection and manipulation of the sleep circuit.
摘要
睡眠稳态维持睡眠和清醒之间的平衡。稳态睡眠调节是
对细胞健康和睡眠障碍至关重要,与许多神经系统疾病和年龄相关的疾病有关。
疾病了解睡眠稳态机制对于开发新的睡眠疗法是必要的
紊乱下丘脑视前区(POA)对睡眠稳态至关重要。多核
POA,包括腹外侧视前区(VLPO)和正中视前核(MnPO),包含睡眠-
与清醒时相比,睡眠时活跃神经元的活动增加。c-Fos阳性细胞数
VLPO和MnPO中的神经元在高睡眠压力下增加,例如在睡眠剥夺后和恢复期间
睡眠剥夺后的睡眠POA中睡眠活跃神经元的完整组成尚不清楚。的
VLPO中表达甘丙肽的GABA能神经元是研究最广泛的睡眠活性神经元。然而,在这方面,
不是所有的c-Fos阳性睡眠活跃神经元都表达甘丙肽,也不是所有的甘丙肽神经元在睡眠过程中都呈c-Fos阳性。
在POA中的任何给定时间睡觉。考虑到POA的分子和功能组成的异质性,
重要的是在单个细胞水平上全面表征POA中的睡眠活跃神经元,
公正的方式。为此,我们将应用最近先进的单核RNA测序(snRNA-
seq)技术与POA进行比较,并比较恢复期间小鼠之间单个细胞中的基因表达变化
睡眠剥夺(高睡眠压力)后的睡眠和长时间自发睡眠(低睡眠压力)后的小鼠
睡眠压力)。Aim 1将全面绘制在高睡眠下激活的所有神经元群
基于一组活动调节基因的压力。我们希望能发现甘丙肽的特殊亚型-
表达抑制性神经元,以及表达其他抑制性神经元的不表达甘丙肽的抑制性神经元组。
神经元标记物在高睡眠压力下被激活。目的2将揭示转录变化的调节
通过在所有细胞群中的稳态睡眠压力,包括神经元和非神经元细胞。比如说,
星形胶质细胞在维持睡眠稳态中起关键作用。然而,人们对转录水平知之甚少。
POA中参与睡眠稳态的星形胶质细胞的调节。鉴于最近发现的分子和
区域特异性的星形胶质细胞,我们假设,我们将揭示区域特异性和细胞特异性的变化,
星形胶质细胞目的3:利用多重荧光原位杂交技术(RNAscope)对肿瘤的解剖结构进行表征,
基于snRNA-seq鉴定的分子标记物对鉴定的睡眠活性神经元进行定位。这
POA中睡眠活跃神经元的分子和空间特征的结合将使未来的研究成为可能。
睡眠回路的解剖和操作
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Xiaofeng Guo其他文献
Xiaofeng Guo的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似国自然基金
基于ADK/Adenosine调控DNA甲基化探讨“利湿化瘀通络”法对2型糖尿病肾病足细胞裂孔膜损伤的干预机制研究
- 批准号:82074359
- 批准年份:2020
- 资助金额:55 万元
- 项目类别:面上项目
细胞外腺苷(Adenosine)作为干细胞旁分泌因子的生物学鉴定和功能分析
- 批准号:81570244
- 批准年份:2015
- 资助金额:57.0 万元
- 项目类别:面上项目
Adenosine诱导A1/A2AR稳态失衡启动慢性低灌注白质炎性损伤及其机制
- 批准号:81171113
- 批准年份:2011
- 资助金额:55.0 万元
- 项目类别:面上项目
相似海外基金
Targeting the A2B Adenosine Receptor for Immunoprevention of Pancreatic Cancer
靶向 A2B 腺苷受体用于胰腺癌的免疫预防
- 批准号:
10929664 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Exploring the role of adenosine A2A receptors in Schizophrenia using opto-pharmacologically controlled allosteric modulation.
利用光药理学控制的变构调节探索腺苷 A2A 受体在精神分裂症中的作用。
- 批准号:
23K14685 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The Role of Adenosine Kinase in Mixed Diastolic Heart Failure and Alzheimer Disease
腺苷激酶在混合性舒张性心力衰竭和阿尔茨海默病中的作用
- 批准号:
10679989 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Allostery-driven G protein selectivity in the adenosine A1 receptor
腺苷 A1 受体中变构驱动的 G 蛋白选择性
- 批准号:
BB/W016974/1 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Research Grant
Investigation of new test methods for adenosine-sensitive atrioventricular block
腺苷敏感型房室传导阻滞新检测方法的探讨
- 批准号:
23K07566 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Probing the role of adenosine pathway in SIV pathogenesis
探讨腺苷途径在 SIV 发病机制中的作用
- 批准号:
10760676 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
The role of A1 adenosine receptor signaling in the decline of S. pneumoniae killing by neutrophils in vaccinated aged hosts
A1 腺苷受体信号传导在疫苗接种老年宿主中中性粒细胞杀伤肺炎链球菌下降中的作用
- 批准号:
10605737 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Adenosine triphosphate as a master variable for biomass in the oceanographic context
三磷酸腺苷作为海洋学背景下生物量的主变量
- 批准号:
2319114 - 财政年份:2023
- 资助金额:
$ 44.69万 - 项目类别:
Standard Grant
Late-Stage Functionalisation of Cyclic Guanosine Monophosphate - Adenosine Monophosphate
环单磷酸鸟苷-单磷酸腺苷的后期功能化
- 批准号:
2751533 - 财政年份:2022
- 资助金额:
$ 44.69万 - 项目类别:
Studentship
Postnatal development of adenosine kinase in the brainstem network that controls breathing
控制呼吸的脑干网络中腺苷激酶的出生后发育
- 批准号:
573323-2022 - 财政年份:2022
- 资助金额:
$ 44.69万 - 项目类别:
University Undergraduate Student Research Awards