The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells
表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用
基本信息
- 批准号:10211467
- 负责人:
- 金额:$ 22.77万
- 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:2021-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqBinding SitesCartilageCell Differentiation processCell LineageCellsCephalicChondrocytesChromatinChromatin Remodeling FactorCompetenceCongenital AbnormalityDNA BindingDevelopmentDevelopmental BiologyDifferentiated GeneEVI1 geneEmbryoEpigenetic ProcessEtiologyExhibitsGene ExpressionGenesGeneticGenetic TranscriptionGenomicsGoalsGrowthHumanKnowledgeLinkMissionMolecularNatureNeural CrestNeural Crest CellNeurogliaNeuronal DifferentiationNeuronsPeripheral Nervous SystemProtein FamilyProteinsPublic HealthRegenerative MedicineRegulationRegulator GenesResearchRoleSeriesSignal TransductionSiteSystemTestingTimeTissuesTranscriptional RegulationTrigeminal SystemUnited States National Institutes of HealthXCL1 geneZebrafishbonecartilage cellcell typechromatin modificationcraniofacialcraniofacial tissuedevelopmental plasticitydisabilityhistone methyltransferasehistone modificationinsightloss of functionmigrationmorphogensmultipotent cellmutantneuromechanismprogenitorrecruitrepairedsingle cell sequencingsingle-cell RNA sequencingstemstem cellstissue repairtranscription factortranscriptometranscriptome sequencing
项目摘要
Summary
How stem progenitor cells maintain plasticity for proper cell fate determination over developmental time is a
fundamental question in developmental biology and regenerative medicine. Cranial neural crest cells (cNCCs)
are an excellent example of a well defined cellular lineage transition in which multipotent cells step through a
series of more restricted progenitors to give rise to diverse array of differentiated cell types, including neurons
and glia of the peripheral nervous system as well as craniofacial cartilage and bone. Thus, understanding the
genetic and epigenetic regulators in cNCC development is key to understanding how cell fate is determined as
well as how cells can be reprogrammed. We hypothesize that the cNCC cartilage/neuron/glial progenitor
retains plasticity through developmental time and cNCC fate acquisition is controlled by regulation of
chromatin accessibility by prdm3. The rationale for the proposed studies is that an in-depth understanding
of the specific factors involved in cNCC lineage transitions will provide insights into both normal developmental
plasticity of cNCCs as well as how progenitors can be reprogramed for tissue repair. We will test this
hypothesis in the following specific aims: 1) Test the hypothesis that prdm3 acts as a molecular cell fate
switch during cNCC differentiation. Here we will test the hypothesis that prdm3 activity is required in cNCCs
cell autonomously to promote the temporal recruitment of progenitors to cartilage by repressing neuronal cell
fate. 2) Test the hypothesis that the cartilage/neuronal/glial (CNG) progenitor retains plasticity through
developmental time and can be reprogramed by loss of prdm3. In Aim 2, hypothesis that CNG
progenitors retain plasticity over developmental time and into larval stages and are reprogramed with loss of
prdm3. 3) Test the hypothesis that Prdm3 regulates the timing of cNCC differentiation by controlling of
genomic accessibility. In Aim 3, we will test the hypothesis that loss of Prdm3 leads to global alterations in
chromatin state at cNCC progenitor genes, which in turn controls the timing of differentiation. Together, these
studies will reveal basic information of how cNCCs differentiate into specific cell types during development.
The results of this proposal have the potential to reveal important new insights into normal developmental
plasticity of cNCCs such that tissue reprograming can be developed for the repair of damaged craniofacial
tissues.
总结
干祖细胞如何在发育过程中保持可塑性以正确决定细胞命运是一个重要的问题。
发育生物学和再生医学的基本问题。颅神经嵴细胞
是一个很好的例子,一个明确的细胞谱系过渡,其中多能细胞通过一个步骤,
一系列更受限制的祖细胞,产生各种分化的细胞类型,包括神经元
和周围神经系统的神经胶质以及颅面软骨和骨。因此,理解
cNCC发育中的遗传和表观遗传调节因子是理解细胞命运如何决定的关键,
以及细胞如何被重新编程。我们假设cNCC软骨/神经元/神经胶质祖细胞
在整个发育过程中保持可塑性,cNCC命运的获得受以下调节的控制:
通过prdm 3的染色质可及性。拟议研究的理由是,深入了解
参与cNCC谱系转换的特定因素将为正常发育和
cNCC的可塑性以及祖细胞如何重新编程用于组织修复。我们将测试这个
1)检验prdm 3作为分子细胞命运的假说
在cNCC分化期间切换。在这里,我们将测试prdm 3活性在cNCC中是必需的这一假设。
通过抑制神经元细胞自主地促进祖细胞向软骨的临时募集
命运2)测试软骨/神经元/神经胶质(CNG)祖细胞通过以下方式保持可塑性的假设:
发育时间,并可以通过prdm 3的丢失重新编程。在目标2中,假设CNG
祖细胞在发育过程中保持可塑性,并进入幼虫阶段,
prdm 3. 3)检验Prdm 3通过控制以下因素来调节cNCC分化的时间的假设:
基因组可及性在目标3中,我们将检验Prdm 3的缺失会导致细胞中的整体改变的假设。
在cNCC祖基因的染色质状态,这反过来控制分化的时机。所有这些
研究将揭示cNCC在发育过程中如何分化为特定细胞类型的基本信息。
这一提议的结果有可能揭示对正常发育的重要新见解。
cNCC的可塑性,以便开发组织重新编程来修复受损的颅面
组织中
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)
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Kristin Artinger其他文献
Kristin Artinger的其他文献
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{{ truncateString('Kristin Artinger', 18)}}的其他基金
The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells
表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用
- 批准号:
10805033 - 财政年份:2023
- 资助金额:
$ 22.77万 - 项目类别:
Reprogramming myogenic regulatory factors in RMS to promote differentiation and halt growth
重新编程 RMS 中的生肌调节因子以促进分化并阻止生长
- 批准号:
10682281 - 财政年份:2023
- 资助金额:
$ 22.77万 - 项目类别:
Genetic and epigenetic regulation of cranial neural crest differentiation
颅神经嵴分化的遗传和表观遗传调控
- 批准号:
10817293 - 财政年份:2023
- 资助金额:
$ 22.77万 - 项目类别:
Genetic and epigenetic regulation of cranial neural crest differentiation
颅神经嵴分化的遗传和表观遗传调控
- 批准号:
10316019 - 财政年份:2021
- 资助金额:
$ 22.77万 - 项目类别:
The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells
表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用
- 批准号:
10352461 - 财政年份:2021
- 资助金额:
$ 22.77万 - 项目类别:
Genetic and epigenetic regulation of cranial neural crest differentiation
颅神经嵴分化的遗传和表观遗传调控
- 批准号:
10442617 - 财政年份:2021
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Mechanistic analysis of novel genetic loci for split hand foot malformation
手足劈裂畸形新基因位点的机制分析
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9906909 - 财政年份:2019
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The mechanisms regulating actin dynamics and polarized membrane transport during cell migration
细胞迁移过程中调节肌动蛋白动力学和极化膜运输的机制
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10536451 - 财政年份:2018
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The mechanisms regulating actin dynamics and polarized membrane transport during cell migration
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10693336 - 财政年份:2018
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Function of chromatin modifiers in cranial neural crest development
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8913662 - 财政年份:2015
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