Molecular Mechanisms of Cell Fate Decisions in Hair Follicle Stem Cells
毛囊干细胞细胞命运决定的分子机制
基本信息
- 批准号:7987181
- 负责人:
- 金额:$ 37.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-09-16 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAddressAdoptedAdultBehaviorBiological AssayBiological ModelsCCL4 geneCell Culture TechniquesCell Fate ControlCell LineageCell MaintenanceCell SeparationCell TransplantationCell surfaceCellsCharacteristicsChromatinClinicCo-ImmunoprecipitationsCultured CellsDNADataDevelopmental GeneDiseaseEnzymesEpigenetic ProcessFrequenciesFutureGene ExpressionGene TargetingGenesGeneticGenomeGenomicsGermGoalsHairHair follicle structureHeterogeneityHistone H2BHistonesHomeostasisImmunofluorescence ImmunologicLabelLightLinkLocationMapsMemoryMessenger RNAMicroarray AnalysisModelingMolecularMorphologyMusNormal tissue morphologyNuclearPathway interactionsPatternPharmaceutical PreparationsPhasePhysiologic pulsePopulationPrecipitationPrevalenceProliferatingRegulationRelative (related person)SkinSorting - Cell MovementStagingStem cellsStructureSystemTestingTetanus Helper PeptideTimeTissuesWestern BlottingWorkadult stem cellbasecell behaviorcell typechromatin immunoprecipitationgene repressiongenome-widehistone modificationinjuredinsightknockout genemRNA Expressionnovelprogenitorprogramspromoterprotein complexprotein protein interactionpublic health relevanceregenerative therapyresearch studyself-renewalstem cell fatestem cell nichestem cell populationtherapeutic targettissue regenerationtooltranscription factor
项目摘要
DESCRIPTION (provided by applicant): Deciphering the molecular mechanisms of adult stem cell (SC) fate decisions is essential for understanding disease and for tissue regenerative therapy. The overall goal of this proposal is to utilize hair follicles and skin as model systems to address at the molecular level the interplay of transcriptional factors and epigenetic regulation in fate choice
decisions of a vertebrate adult stem cell population in its native tissue. Because hair
follicle stem cells synchronously proliferate and return to quiescence in the mouse skin,
this system allows mechanistic insight that is otherwise more difficult to achieve. In Aim
(1) we plan to investigate in more depth the relationship between more dormant versus
more active cell subpopulations in the hair follicle stem cell niche, by characterizing their
morphogenetic and self-renewal ability in cell culture and cell transplantation assays.
The existence of these two kinds of cell subpopulations in stem cell niches appears to be
a relatively common feature for at least several vertebrate tissues. Their interplay in
maintaining tissue homeostasis is important for accurate description of stem cell
behavior and fate decisions. In Aim (2) we will examine the distribution of histone marks
across the genome at two stages of stem cell activity by chromatin immuno-precipitation
and sequencing, and attempt to examine a potential link between two known adult tissue
stem cells features: quiescence and plasticity. In Aim (3) we will employ two
transcription factors Runx1 and Gata6 as fate acquisition regulators. We will test their
potential implication in remodeling the stem cell histone epigenome via interactions with
a battery of histone modifying enzymes we found expressed in the hair follicle in a
relevant pattern. We will induce acute loss of Runx1 and Gata6 in mouse skin and
examine the mRNA expression level of specific histone modifying enzymes in the
relevant hair follicle cell populations. In addition we will perform co-immunoprecipitation
or pull-down experiments to examine a potential direct protein-protein interaction
between Runx1 or Gata6 and specific histone modifying enzymes. This will begin to
address the mechanisms of fate acquisition in a vertebrate adult stem cell population
and shed light on the interplay between transcription factors that work as master
regulator in orchestrating cell fate and global remodeling of histone epigenetic marks.
PUBLIC HEALTH RELEVANCE: A large number of diseases are due to miss-regulation of cell fate acquisition of adult tissue stem cells during their activity to maintain normal tissue homeostasis. There has been recently great promise for developing novel drug therapeutics that target specific histone modifying enzymes, some already present in clinics. This proposal seeks to utilize a versatile vertebrate model system, mouse skin and hair follicles, to gain better understanding of the interplay between histone epigenetic marks and transcription factors that control cell fate decisions in adult vertebrate stem cells.
描述(由申请人提供):破解成体干细胞(SC)命运决定的分子机制对于理解疾病和组织再生治疗至关重要。本研究的总体目标是利用毛囊和皮肤作为模型系统,在分子水平上解决转录因子和表观遗传调控在命运选择中的相互作用
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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{{ truncateString('Tudorita Tumbar', 18)}}的其他基金
Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin
研究小鼠皮肤成年毛发周期中协调的内皮-上皮相互作用
- 批准号:
10674132 - 财政年份:2023
- 资助金额:
$ 37.71万 - 项目类别:
Defining the heterogeneity of cell lineages in the inter-follicular epidermis
定义毛囊间表皮细胞谱系的异质性
- 批准号:
10596423 - 财政年份:2023
- 资助金额:
$ 37.71万 - 项目类别:
Tissue regeneration studies by controlled H3 K4/9/27me3 levels in adult mouse skin
通过控制成年小鼠皮肤中的 H3 K4/9/27me3 水平进行组织再生研究
- 批准号:
9903233 - 财政年份:2018
- 资助金额:
$ 37.71万 - 项目类别:
Tissue regeneration studies by controlled H3 K4/9/27me3 levels in adult mouse skin
通过控制成年小鼠皮肤中的 H3 K4/9/27me3 水平进行组织再生研究
- 批准号:
10394721 - 财政年份:2018
- 资助金额:
$ 37.71万 - 项目类别:
Defining the heterogeneity of cell lineages in the inter-follicular epidermis
定义毛囊间表皮细胞谱系的异质性
- 批准号:
9894755 - 财政年份:2017
- 资助金额:
$ 37.71万 - 项目类别:
Identifying bio-markers for putative epidermal stem cells in mouse skin.
识别小鼠皮肤中假定的表皮干细胞的生物标志物。
- 批准号:
8827677 - 财政年份:2014
- 资助金额:
$ 37.71万 - 项目类别:
Slowly cycling cells and hair follicle stem cells
缓慢循环细胞和毛囊干细胞
- 批准号:
7847291 - 财政年份:2009
- 资助金额:
$ 37.71万 - 项目类别:
Molecular Mechanisms of Cell Fate Decisions in Hair Follicle Stem Cells
毛囊干细胞细胞命运决定的分子机制
- 批准号:
8821797 - 财政年份:2005
- 资助金额:
$ 37.71万 - 项目类别:
Slowly cycling cells and hair follicle stem cells
缓慢循环细胞和毛囊干细胞
- 批准号:
7664493 - 财政年份:2005
- 资助金额:
$ 37.71万 - 项目类别:
Slowly cycling cells and hair follicle stem cells
缓慢循环细胞和毛囊干细胞
- 批准号:
7275617 - 财政年份:2005
- 资助金额:
$ 37.71万 - 项目类别:
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