Mechanism of niche formation, and impact of niche position on tissue function
生态位形成机制及生态位位置对组织功能的影响
基本信息
- 批准号:10604532
- 负责人:
- 金额:$ 4.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-26 至 2025-09-25
- 项目状态:未结题
- 来源:
- 关键词:AblationAddressAdhesionsAffectApoptosisAtrophicBehaviorBiological AssayCancerousCell AdhesionCell CommunicationCellsCommunicationCompanionsCompetenceCuesDataDefectDevelopmentDorsalDrosophila genusEctopic ExpressionEmbryonic DevelopmentEnvironmentEquilibriumFacultyFeedbackFellowshipFunctional disorderGlandGleanHealthHematopoieticHematopoietic stem cellsHemocytesHomeostasisHumanHyperactivityImageImmuneImmune responseInfectionLarvaLateralMaintenanceMeasuresMentorshipMesodermModelingMorphogenesisNatural ImmunityNutrientOrganismPennsylvaniaPopulationPositioning AttributePrimordiumRNA InterferenceRegulationReproducibilityResearchResearch TrainingRoleSignal TransductionSpecific qualifier valueStructureSurfaceTestingTestisTissuesTrainingTransducersUniversitiesVisceralWaspscareercell motilitycell typeexperienceimprovedknock-downlymph nodesmigrationmutantoverexpressionprogenitorprospectiveself-renewalsingle-cell RNA sequencingstem cell differentiationstem cellssymposiumtumorwound healing
项目摘要
Project Summary/Abstract
Understanding how niches regulate stem cells is critical to human health because aberrant regulation by the
niche can cause tumor formation or tissue atrophy. Well-studied niches form in predictable structures following
reproducible morphogenetic changes, suggesting niche structure is regulated and functionally important. This
has not been directly studied. Additionally, the mechanisms that determine the initial positioning of niches during
development remain understudied. To address these deficits, we study the Drosophila posterior signaling center
(PSC)—the niche of the larval lymph gland. The PSC maintains hematopoietic progenitors, and it induces
differentiation of a special immune cell upon immune challenge. The PSC forms during embryogenesis: its cells
migrate dorsally, where they ultimately reside, coalesced at the lymph gland posterior. Preliminary data indicates
that mutants without visceral mesoderm (vm) have dispersed PSCs and fewer PSC cells. As such, the overall
hypothesis is that the vm guides PSC positioning to the lymph gland posterior. We further hypothesize that a
coalesced PSC is required for its optimal function as a niche. Aim 1 will identify the role of vm and its mechanism
of action in instructing PSC formation via live-imaging of vm mutants to identify the timing and type of the PSC
defect, and then testing vm candidate cues with vm-specific RNAi knockdown of the cue followed by analysis of
PSC positioning. The PSC signal transducer will be identified by PSC-specific RNAi knockdown of candidate
transducers. Ectopic expression of the vm cue in a nearby tissue will reveal if the cue is a true guidance cue
sufficient to guide PSC positioning, or whether it confers competency to respond to other positional cues. Aim 2
will investigate how PSC coalescence contributes to niche function by causing PSC dispersion and then
assessing PSC functions. Ability of the dispersed PSC to maintain progenitors will be tested by quantitating PSC-
dependent progenitors, and ability to generate an immune response by challenging larvae with parasitoid wasp
infection, and then quantitating a specialized immune cell type. The PSC can sense the organism’s nutrient and
immune environment, but it is unknown if it senses feedback from the cells it regulates. This will be tested with
lineage-specific ablation of progenitors or mature hemocytes in the lymph gland with Gal4/UAS-driven apoptosis.
Then the level of PSC maintenance and differentiation signals will be measured for comparison to controls.
Accomplishing these aims will reveal principles of niche formation, how niche structure impacts its function, and
whether a niche receives feedback from the tissue it supports. Research training will take place at the University
of Pennsylvania under the advisement of the Sponsor, the PI’s thesis committee, and Penn faculty as needed.
The training plan consists of an integrated and creatively unique sequence of mentorship experiences to prepare
the PI for their career. Training includes several opportunities to improve written and verbal communication, and
professional development activities (course, conferences, seminars) for the PI to transition to a new research
topic for an academic postdoctoral fellowship.
项目总结/文摘
项目成果
期刊论文数量(0)
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Kara Nelson其他文献
Kara Nelson的其他文献
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{{ truncateString('Kara Nelson', 18)}}的其他基金
Mechanism of niche formation, and impact of niche position on tissue function
生态位形成机制及生态位位置对组织功能的影响
- 批准号:
10710395 - 财政年份:2022
- 资助金额:
$ 4.68万 - 项目类别:
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