Deciphering the role of p16INK4A+ fibroblasts in lung fibrosis
解读 p16INK4A 成纤维细胞在肺纤维化中的作用
基本信息
- 批准号:10559515
- 负责人:
- 金额:$ 55.69万
- 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:2022-02-01 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccelerationAddressAdoptive Cell TransfersAdoptive TransferAgingAlveolusAreaBiological AssayBiological MarkersBiologyCDKN2A geneCell Cycle ArrestCell LineCell SeparationCellsCharacteristicsChemicalsChronic lung diseaseCicatrixCollagenCuesDataDiseaseDisease modelDrug ScreeningElderlyEngineeringEpitheliumExhibitsFibroblastsFibrosisGeneticGenetic ModelsHumanImageIn VitroInduction of ApoptosisInflammatoryInjuryKnowledgeLigandsLungMaintenanceMetaplasiaMethodologyModelingMorphologyMusOrganOrganoidsOutcomePathogenesisPathologicPathologyPhenotypePhysiologicalProcessPulmonary FibrosisRegenerative responseReporterReportingRisk FactorsRoleTestingTherapeuticTimeTissuesTractionTransplantationTumor Suppressor ProteinsUncertaintyValidationage relatedagedcell behaviorcell typecombinatorialdefined contributionepithelial stem cellfibrotic lungfibrotic lung diseasefunctional declinegenetic approachhigh throughput screeningidiopathic pulmonary fibrosisin vivolung injurymigrationnovelprogenitorprogramsprospectiverational designregenerative cellresponsescreeningsenescencesingle cell analysissingle-cell RNA sequencingstem cellstherapeutic targettooltumorigenesiswound healing
项目摘要
Project Summary/Abstract
Aging is one of the biggest risk factors for many chronic lung diseases, including idiopathic pulmonary fibrosis
(IPF). However, uncertainties remain as to how age-related processes contribute to the pathogenesis of IPF,
particularly in deciphering the cell types that might play a role in both aging and fibrotic transformation.
Senescence, a cellular state characterized by an irreversible cell cycle arrest and other morphologic
transformations, is thought to be a cellular phenotype that becomes increasingly prevalent in aged organs,
contributing to the decline in function over time. p16INK4A, a tumor suppressor, is one of the best-studied
biomarkers of senescent cells in vitro and in vivo. Numerous genetic models have been built to remove p16INK4A+
cells from tissues, demonstrating a functional role for these cells in promoting age-related pathologies such as
lung fibrosis. Despite the knowledge gained from strategies that remove p16INK4A+ cells, deletion of these cells
precludes the identification and functional characterization of p16INK4A+ cells in vivo, leaving a large gap in our
understanding of how senescent cells might behave in tissues rather than in a culture dish. To address this, we
constructed a novel genetic reporter of senescence by engineering an amplified fluorescent tag driven by
expression of p16INK4A (mouse referred to as INK4A H2B-GFP Reporter-In-Tandem, or INKBRITE) to isolate and
characterize p16INK4A+ cells in vivo and ex vivo. To our surprise, we were able to identify p16INK4A+ fibroblasts in
young and healthy lungs that contribute to scar-forming cells in areas of fibrotic remodeling. Furthermore,
p16INK4A+ cells are able to alter the epithelial progenitor microenvironment and alter stem cell regenerative
outcomes. This led us to the hypothesis that p16INK4A+ fibroblasts are capable of contributing to fibrosis by
forming scars and inducing an pathologic epithelial response, and the INKBRITE reporter could be leveraged as
a screening platform to identify compounds that more precisely target p16INK4A+ fibroblasts in vivo. Through the
use of single cell RNA sequencing, adoptive cell transfers, lineage tracing, high-content imaging, and various
methodologies outlined in this proposal, we aim to better define the cellular contribution of p16INK4A+ fibroblasts
to fibrotic transformation, and define agents that might better remove it from tissues.
项目总结/文摘
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 }}
Tien Peng其他文献
Tien Peng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('Tien Peng', 18)}}的其他基金
Deciphering the role of p16INK4A+ fibroblasts in lung fibrosis
解读 p16INK4A 成纤维细胞在肺纤维化中的作用
- 批准号:
10340480 - 财政年份:2022
- 资助金额:
$ 55.69万 - 项目类别:
Mesenchymal modulation of epithelial metaplasia in lung fibrosis
肺纤维化中上皮化生的间充质调节
- 批准号:
10548148 - 财政年份:2021
- 资助金额:
$ 55.69万 - 项目类别:
Mesenchymal modulation of epithelial metaplasia in lung fibrosis
肺纤维化中上皮化生的间充质调节
- 批准号:
10331772 - 财政年份:2021
- 资助金额:
$ 55.69万 - 项目类别:
Mesenchymal modulation of epithelial metaplasia in lung fibrosis
肺纤维化中上皮化生的间充质调节
- 批准号:
10095587 - 财政年份:2021
- 资助金额:
$ 55.69万 - 项目类别:
The roles of Hedgehog signaling in pulmonary vascular development and remodeling
Hedgehog信号在肺血管发育和重塑中的作用
- 批准号:
9118452 - 财政年份:2014
- 资助金额:
$ 55.69万 - 项目类别:
The roles of Hedgehog signaling in pulmonary vascular development and remodeling
Hedgehog信号在肺血管发育和重塑中的作用
- 批准号:
9300965 - 财政年份:2014
- 资助金额:
$ 55.69万 - 项目类别:
The roles of Hedgehog signaling in pulmonary vascular development and remodeling
Hedgehog信号在肺血管发育和重塑中的作用
- 批准号:
8766755 - 财政年份:2014
- 资助金额:
$ 55.69万 - 项目类别:
相似海外基金
EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
- 批准号:
NE/Y000080/1 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Research Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328975 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Continuing Grant
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
- 批准号:
2400967 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Standard Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
- 批准号:
10112700 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328973 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328972 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332916 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332917 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Standard Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328974 - 财政年份:2024
- 资助金额:
$ 55.69万 - 项目类别:
Continuing Grant
Study of the Particle Acceleration and Transport in PWN through X-ray Spectro-polarimetry and GeV Gamma-ray Observtions
通过 X 射线光谱偏振法和 GeV 伽马射线观测研究 PWN 中的粒子加速和输运
- 批准号:
23H01186 - 财政年份:2023
- 资助金额:
$ 55.69万 - 项目类别:
Grant-in-Aid for Scientific Research (B)