Transcriptome and Network Analysis of Cleft Palate
腭裂的转录组和网络分析
基本信息
- 批准号:10539242
- 负责人:
- 金额:$ 79.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-01 至 2023-09-15
- 项目状态:已结题
- 来源:
- 关键词:AdhesionsAffectAgeAnteriorBindingBiologicalBiomechanicsCRISPR/Cas technologyCellsCleft PalateClinicalComplexComputational BiologyCongenital AbnormalityCritical PathwaysDataData SetDefectDevelopmentDevelopmental BiologyDiagnosisDiseaseEmbryoEpitheliumEtiologyEventFGFR2 geneFibroblast Growth FactorGene ExpressionGene Expression ProfileGene Expression ProfilingGenesGeneticGenetic TranscriptionGenotypeGoalsGrowthHumanImmunohistochemistryIn Situ HybridizationIndividualInternetInterventionIntuitionKnock-inKnockout MiceLibrariesLinkLiteratureMapsMaxillaMedialMediatingMedicalMesenchymalMesenchymeMethodsModelingMolecularMorphogenesisMorphologyMovementMultiomic DataMusMutant Strains MiceMutationOperative Surgical ProceduresOrgan Culture TechniquesOutcomePalatePathologicPathway AnalysisPathway interactionsPatternPopulationPreventionProcessPropertyPsychosocial Assessment and CareRNARNA SplicingResolutionRoleSHH geneSeriesSignal PathwaySignal TransductionStructural Congenital AnomaliesStructureSystemSystems BiologyTechnologyTissue-Specific Gene ExpressionTissuesValidationWild Type MouseWorkadvanced systemcell typecraniofacialdifferential expressiongene discoveryhuman modelimprovedin silicoin vivoinnovationinsightmolecular scalemouse modelmutantmutant mouse modelnetwork modelsnovelnull mutationoral cleftorofacial cleftpalatal shelvespalatogenesispreventpsychosocialsimulationsingle cell sequencingsingle-cell RNA sequencingtooltranscription factortranscriptometranscriptome sequencingtranscriptomics
项目摘要
ABSTRACT
Cleft palate is one of the most common structural birth defects. Surgical correction and medical and psychosocial
care impose significant personal and societal burdens. Increased understanding of the etiology of cleft palate
potentially will lead to improvements in diagnosis and treatment. Palatogenesis is enormously complex. Paired
palatal shelves first extend vertically from the maxillary processes and must grow sufficiently so that upon
horizontal elevation their medial edges come into contact. Epithelia covering the medial shelves disintegrate,
allowing their fusion. Key processes involved include epithelial/mesenchymal interactions and transitions.
Studies in humans and mice have identified at least 429 genes associated with oral clefting. Reductionist
scientific approaches have provided detail about individual genes and pathways in palatogenesis, but the intuitive
models generated are not sufficient to represent the enormous complexity of the process. We will employ
transcriptome and network analyses to understand how biological components work together to produce system-
wide outcomes of epithelial differentiation and adhesion, mesenchymal biomechanical properties affecting
remodeling and shelf elevation, and anterior/posterior regionalization of epithelia and mesenchyme. These
processes require the integration of multiple cross-regulating signaling pathways. Fibroblast growth factor (FGF)
and sonic hedgehog (SHH) are two such pathways, and their information is integrated with other pathways by
the transcription factor p63. We will generate bulk and single-cell RNA-seq libraries from the palatal shelves of
wild type mice to discover gene coexpression and regulatory networks, and specific cell populations involved in
normal palatogenesis. For bulk RNA-seq libraries we will separate anterior and posterior epithelial and
mesenchymal compartments allowing region-specific analysis of transcriptional changes. We will use the same
approach for four mutant mouse lines, exploiting these gene perturbations to identify key driver genes and
interacting pathways within these networks. We will study two activating FGFR2 mutations that exert their
differential effects from the epithelium or the mesenchyme (S252W or C342Y) and null mutations of SHH and
p63, expressed in the epithelium. Complementary bulk and single-cell RNA-seq libraries will identify differential
gene expression and novel key components and pathways critical to palatogenesis. We will use these datasets,
in conjunction with publicly available palate-related datasets to build high-resolution, multiscale molecular
networks that will be used to develop predictive, mechanistic models of palatogenesis. Novel molecular networks
and key regulators identified through the multiscale network modeling approach will be validated by in situ
hybridization, immunohistochemistry, palatal organ cultures, and mouse models. Our innovative approach to
generating comprehensive datasets, using advanced systems biology technologies, and building multiscale
network models of normal and abnormal palatogenesis will have a large impact on the clinical, craniofacial,
-omics, and developmental biology fields.
摘要
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 }}
Ethylin Wang Jabs其他文献
Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans
患有黑棘皮病的克鲁宗综合征中的成纤维细胞生长因子受体 3(FGFR3)跨膜突变
- DOI:
10.1038/ng1295-462 - 发表时间:
1995-12-01 - 期刊:
- 影响因子:29.000
- 作者:
Gregory A. Meyers;Seth J. Orlow;Ian R. Munro;Kelly A. Przylepa;Ethylin Wang Jabs - 通讯作者:
Ethylin Wang Jabs
Aural atresia associated with multiple congenital anomalies and mental retardation: A new syndrome
- DOI:
10.1016/s0022-3476(87)80017-3 - 发表时间:
1987-05-01 - 期刊:
- 影响因子:
- 作者:
Linda F. Cooper;Ethylin Wang Jabs - 通讯作者:
Ethylin Wang Jabs
亚洲人群FOXF2基因多核苷酸多态位点与非综合征型唇腭裂关联的新证据
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
Bo Zhang;Ethylin Wang Jabs;Alan F. Scott;Terri H. Beaty - 通讯作者:
Terri H. Beaty
国际唇腭裂研究小组数据的基因及基因环境交互作用联合研究关于亚洲人群BMP4基因与非综合征型唇腭裂关联的新证据
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:3.7
- 作者:
Ethylin Wang Jabs;Margaret M. Parker;Alan F. Scott;Terri H. Beaty - 通讯作者:
Terri H. Beaty
A genome wide screen of Crohn's disease in a large pedigree shows evidence for linkages to chromosomes 11, 16, 8 and 15
- DOI:
10.1016/s0016-5085(98)83831-6 - 发表时间:
1998-04-15 - 期刊:
- 影响因子:
- 作者:
Steven R. Brant;Dan Nicolae;Michele C. LaBuda;Romulo Baltazar;Carter Fields;Geoffrey Ravenhill;Mike Pickles;Patrick M. Rohal;Ethylin Wang Jabs;Stephen B. Hanauer;Theodore M. Bayless;Judy H. Cho - 通讯作者:
Judy H. Cho
Ethylin Wang Jabs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 }}
{{ truncateString('Ethylin Wang Jabs', 18)}}的其他基金
Cartilage and bone of the lower jaw in development and disease
下颌软骨和骨骼的发育和疾病
- 批准号:
10552606 - 财政年份:2022
- 资助金额:
$ 79.34万 - 项目类别:
Cartilage and bone of the lower jaw in development and disease
下颌软骨和骨骼的发育和疾病
- 批准号:
10357271 - 财政年份:2022
- 资助金额:
$ 79.34万 - 项目类别:
Genetic, Tissue, and Anatomical Interactions in Mandibulofacial Dysmorphogenesis
下颌面部畸形发生中的遗传、组织和解剖学相互作用
- 批准号:
10220643 - 财政年份:2021
- 资助金额:
$ 79.34万 - 项目类别:
Genetic, Tissue, and Anatomical Interactions in Mandibulofacial Dysmorphogenesis
下颌面部畸形发生中的遗传、组织和解剖学相互作用
- 批准号:
10663868 - 财政年份:2021
- 资助金额:
$ 79.34万 - 项目类别:
Genetic, Tissue, and Anatomical Interactions in Mandibulofacial Dysmorphogenesis
下颌面部畸形发生中的遗传、组织和解剖学相互作用
- 批准号:
10470325 - 财政年份:2021
- 资助金额:
$ 79.34万 - 项目类别:
Transcriptome and Network Analysis of Cleft Palate
腭裂的转录组和网络分析
- 批准号:
10314049 - 财政年份:2020
- 资助金额:
$ 79.34万 - 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
- 批准号:
10159749 - 财政年份:2013
- 资助金额:
$ 79.34万 - 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
- 批准号:
9260707 - 财政年份:2013
- 资助金额:
$ 79.34万 - 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
- 批准号:
9751946 - 财政年份:2013
- 资助金额:
$ 79.34万 - 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
- 批准号:
8640965 - 财政年份:2013
- 资助金额:
$ 79.34万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 79.34万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 79.34万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 79.34万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 79.34万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 79.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 79.34万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 79.34万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 79.34万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 79.34万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 79.34万 - 项目类别:
Miscellaneous Programs