The Role of Retinal Progenitor microRNAs for Late-stage Progenitor Cell State and Muller Glia Reprogramming
视网膜祖细胞 microRNA 在晚期祖细胞状态和 Muller 胶质细胞重编程中的作用
基本信息
- 批准号:10366875
- 负责人:
- 金额:$ 40.5万
- 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:2022-03-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:3&apos Untranslated Regions3-DimensionalAddressAge related macular degenerationArchitectureBindingBiological AssayBlindnessCell CycleCell ProliferationCell physiologyCellsCyclin D1DataDevelopmentDicer EnzymeDiseaseDisease ProgressionElectrophysiology (science)FishesGene ExpressionGene Expression ProfileGenerationsGenesGoalsIn VitroIonsLeadMalignant NeoplasmsMeasuresMessenger RNAMicroRNAsMolecularMonitorMorphologyMuller&aposs cellMusNatural regenerationNeural RetinaNeurogliaNeuronsOrganismPathologicPhotoreceptorsPlayProliferatingPropertyRegenerative MedicineRegulationReporterResourcesRetinaRetinal DegenerationRetinal DiseasesRetinitis PigmentosaRodRoleSourceSupplementationTestingTherapeutic AgentsTherapeutic UsesTissuesValidationVisual impairmentWorkantagonistbasebiomarker identificationcell behaviorcell fate specificationcell replacement therapycell typeexperimental studyin vivoinnovationoverexpressionpatch clamppostnatalpostnatal developmentpreservationpreventrepairedrestorationretinal neuronretinal progenitor cellretinal rodsretinogenesissensorsight restorationsingle-cell RNA sequencingstem cell therapystem cellstherapy developmenttooltranscription factortransplantation therapy
项目摘要
PROJECT SUMMARY
Our long-term goal is to prevent blindness, either by interfering with disease progression or by developing cell
replacement therapies to restore vision. We believe that microRNAs (miRNAs) are a very powerful and innovative
tool to accomplish this, but we first need to identify the set of miRNAs required for retinal cell fate specification
and proper cell function in the developing retina. These miRNAs might represent potential therapeutic agents to
not only restore imbalances that occur with the onset of retinal disorders, but also to induce specific cell fates for
Müller glia (MG) reprogramming. We therefore propose to investigate the role of retinal progenitor cell (RPC)-
miRNAs for late-stage RPC state and function and MG reprogramming by Aim 1: identifying the specific miRNAs
required in early postnatal development, when rod photoreceptors (PR), bipolar cells (BCs), and MG are
generated. Aim 2: testing miRNAs to reprogram MG into functional retinal neurons with focus on BCs and rod
PR. We propose to use a mouse line that will not be able to produce miRNAs in their RPCs to better understand
the function of miRNAs in retinal development and diseases. We will analyze tissue and cells with regard to
morphological and functional alterations and determine which miRNAs are responsible for changes in cellular
behavior. If we discover certain cell types that do not form properly without miRNAs, this could mean that specific
miRNAs are required for proper development of that cell type. Rescue experiments will show whether disturbed
tissue can be restored by miRNA supplementation and would imply potential therapeutic use. These miRNAs
might also be new, additional reprogramming factors to regenerate specific cell types from stem cells or MG. My
previous work has shown that miRNAs can reprogram MG into neuronal-like cells similar to BCs. However,
whether these reprogrammed neurons are functional, and whether other neurons are generated, is still unknown.
To address these questions, we will reprogram primary MG from reporter mice to visualize the conversion of MG
into RPCs and neuronal-like cells, use patch clamp to measure ion currents, and profile their gene expression.
miRNA candidates that successfully converted MG into functional neurons will be tested subsequently in 3D
organotypic cultures (intact retinas outside the organism). Explants will be treated with miRNAs and evaluated
with regard to cell proliferation and proper differentiation capability. miRNA candidates that can induce MG
reprogramming ex vivo will be utilized for in vivo reprogramming approaches. To reveal underlying mechanisms
and true miRNAs targets, we will use target prediction and target validation tools to narrow down and test
selected candidates via sensors (in vitro proof of miRNA:mRNA prediction) and rescue experiments. This work
provides a comprehensive study of miRNAs by combining molecular and cellular analyses with functional testing,
in vitro, ex vivo and in vivo and will reveal (1) the set miRNAs required for proper retinal development and cell
fate specification of late-born retinal neurons and (2) the set of miRNAs that can reprogram MG into functional
neurons.
项目总结
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 }}
Stefanie G Wohl其他文献
Stefanie G Wohl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('Stefanie G Wohl', 18)}}的其他基金
The Role of Retinal Progenitor microRNAs for Late-stage Progenitor Cell State and Muller Glia Reprogramming
视网膜祖细胞 microRNA 在晚期祖细胞状态和 Muller 胶质细胞重编程中的作用
- 批准号:
10570874 - 财政年份:2022
- 资助金额:
$ 40.5万 - 项目类别:
相似海外基金
Impact of alternative polyadenylation of 3'-untranslated regions in the PI3K/AKT cascade on microRNA
PI3K/AKT 级联中 3-非翻译区的替代多聚腺苷酸化对 microRNA 的影响
- 批准号:
573541-2022 - 财政年份:2022
- 资助金额:
$ 40.5万 - 项目类别:
University Undergraduate Student Research Awards
How do untranslated regions of cannabinoid receptor type 1 mRNA determine receptor subcellular localisation and function?
1 型大麻素受体 mRNA 的非翻译区如何决定受体亚细胞定位和功能?
- 批准号:
2744317 - 财政年份:2022
- 资助金额:
$ 40.5万 - 项目类别:
Studentship
MICA:Synthetic untranslated regions for direct delivery of therapeutic mRNAs
MICA:用于直接递送治疗性 mRNA 的合成非翻译区
- 批准号:
MR/V010948/1 - 财政年份:2021
- 资助金额:
$ 40.5万 - 项目类别:
Research Grant
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10019570 - 财政年份:2019
- 资助金额:
$ 40.5万 - 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10223370 - 财政年份:2019
- 资助金额:
$ 40.5万 - 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10455108 - 财政年份:2019
- 资助金额:
$ 40.5万 - 项目类别:
Synergistic microRNA-binding sites, and 3' untranslated regions: a dialogue of silence
协同的 microRNA 结合位点和 3 非翻译区:沉默的对话
- 批准号:
255762 - 财政年份:2012
- 资助金额:
$ 40.5万 - 项目类别:
Operating Grants
Analysis of long untranslated regions in Nipah virus genome
尼帕病毒基因组长非翻译区分析
- 批准号:
20790351 - 财政年份:2008
- 资助金额:
$ 40.5万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Search for mRNA elements involved in the compatibility between 5' untranslated regions and coding regions in chloroplast translation
寻找参与叶绿体翻译中 5 非翻译区和编码区之间兼容性的 mRNA 元件
- 批准号:
19370021 - 财政年份:2007
- 资助金额:
$ 40.5万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Post-transcriptional Regulation of PPAR-g Expression by 5'-Untranslated Regions
5-非翻译区对 PPAR-g 表达的转录后调控
- 批准号:
7131841 - 财政年份:2006
- 资助金额:
$ 40.5万 - 项目类别: