Non-coding RNA In Stem Cell Biology
干细胞生物学中的非编码 RNA
基本信息
- 批准号:10451518
- 负责人:
- 金额:$ 41.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-03 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAgingAnimalsBindingBiologyCell Differentiation processCellsChromatinCongenital AbnormalityEmbryonic DevelopmentFailureFertilityFunctional disorderGene Expression RegulationGenome StabilityGerm CellsGoalsIn VitroInfertilityMalignant NeoplasmsMediatingMolecularNatural regenerationOutcomePathway interactionsPlanariansPluripotent Stem CellsPopulationProcessProteinsRNARegulationRoleSmall RNATherapeuticUntranslated RNAin vivoinsightpluripotencystem cell biologystem cell functionstem cellstargeted treatment
项目摘要
PROJECT SUMMARY
Pluripotent stem cells are essential during early embryonic development, and hold great potential for
therapeutic applications. In both cases, correct regulation of division and differentiation of these cells is crucial
for a favorable outcome. Currently, there are major gaps in our understanding of how stem cells maintain their
pluripotent state, or make the transition to differentiation. Several types of non-coding RNA are enriched in
stem cells, and have been proposed to function in these regulatory processes, in particular by affecting the
chromatin state of the cells. We will leverage a prolific population of adult pluripotent stem cells, the neoblasts
of the planarian Schmidtea mediterranea, to address the role and mechanism of two types of non-coding RNA
in in vivo stem cell biology. One branch of this project concerns the role of long non-coding RNAs (lncRNAs) in
pluripotency and differentiation. Whereas many in vitro screens have suggested a role for lncRNAs in the
regulation surrounding pluripotency, few cases of in vivo effects have been demonstrated. We will use an in
vivo screen of planarian stem cell function to first identify functionally important lncRNAs, which will then be
studied further mechanistically. This will allow us to focus our efforts on the most relevant examples of lncRNA-
mediated stem cell regulation. The other branch of this project focuses on the role of PIWI-interacting RNAs
(piRNAs), and their binding partners the PIWI proteins, in stem cell biology. These small RNAs are mostly
known for their role in transposon silencing in the animal germline, but are also essential for stem cell function,
especially in regenerating animals. We aim to determine what the basis for that requirement is, by determining
which stages of stem cell biology are affected and what the consequences of failure of the piRNA pathway are.
Furthermore several aspects of piRNA function are not easily addressed in germ cells, and we will use the
planarian stem cells to further our understanding of those mechanistic aspects of piRNA biology. This project
will provide new insights in non-coding RNA function and mechanism, and will have broad impact on our
understanding of pluripotent stem cells and regulation of genomic stability in general. These insights are
essential for the safe use of pluripotent cells in therapeutic applications, as well as for targeted treatment of
conditions related dysfunction of endogenous stem cells including forms of infertility, birth defects, and aging.
Furthermore, this project has relevance to conditions related to loss of cell identity, such as cancer.
项目概要
多能干细胞在早期胚胎发育过程中至关重要,并且具有巨大的潜力
治疗应用。在这两种情况下,正确调节这些细胞的分裂和分化至关重要
以获得有利的结果。目前,我们对干细胞如何维持其功能的理解还存在重大差距。
多能状态,或向分化过渡。多种类型的非编码RNA富含
干细胞,并已被提议在这些调节过程中发挥作用,特别是通过影响
细胞的染色质状态。我们将利用大量的成体多能干细胞,即新生细胞
涡虫 Schmidtea mediterranea 的研究,探讨两种非编码 RNA 的作用和机制
在体内干细胞生物学中。该项目的一个分支涉及长非编码 RNA (lncRNA) 在
多能性和分化。尽管许多体外筛选表明 lncRNA 在
围绕多能性的调节,很少有体内效应的案例已被证明。我们将使用一个 in
涡虫干细胞功能的体内筛选,首先鉴定功能重要的 lncRNA,然后将其
进一步进行了机械研究。这将使我们能够将精力集中在 lncRNA 最相关的例子上
介导的干细胞调节。该项目的另一个分支重点关注 PIWI 相互作用 RNA 的作用
(piRNA)及其在干细胞生物学中的结合伙伴 PIWI 蛋白。这些小RNA大多是
以其在动物种系中转座子沉默中的作用而闻名,但对于干细胞功能也至关重要,
尤其是在再生动物中。我们的目标是通过确定该要求的基础是什么
干细胞生物学的哪些阶段受到影响以及 piRNA 途径失败的后果是什么。
此外,piRNA 功能的几个方面在生殖细胞中不容易解决,我们将使用
涡虫干细胞进一步我们对 piRNA 生物学机制的理解。这个项目
将为非编码RNA功能和机制提供新的见解,并将对我们的研究产生广泛影响
了解多能干细胞和基因组稳定性的一般调节。这些见解是
对于在治疗应用中安全使用多能细胞以及靶向治疗至关重要
与内源干细胞功能障碍相关的疾病,包括不孕症、出生缺陷和衰老。
此外,该项目还与细胞身份丧失相关的疾病相关,例如癌症。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum.
- DOI:10.3390/ijms24021051
- 发表时间:2023-01-05
- 期刊:
- 影响因子:5.6
- 作者:Poulet, Axel;Rousselot, Ellyn;Teletchea, Stephane;Noirot, Celine;Jacob, Yannick;van Wolfswinkel, Josien;Thiriet, Christophe;Duc, Celine
- 通讯作者:Duc, Celine
PIWI-mediated control of tissue-specific transposons is essential for somatic cell differentiation.
- DOI:10.1016/j.celrep.2021.109776
- 发表时间:2021-10-05
- 期刊:
- 影响因子:8.8
- 作者:Li D;Taylor DH;van Wolfswinkel JC
- 通讯作者:van Wolfswinkel JC
Chromatin analysis of adult pluripotent stem cells reveals a unique stemness maintenance strategy.
- DOI:10.1126/sciadv.adh4887
- 发表时间:2023-10-06
- 期刊:
- 影响因子:13.6
- 作者:Poulet, Axel;Kratkiewicz, Arcadia J.;Li, Danyan;van Wolfswinkel, Josien C.
- 通讯作者:van Wolfswinkel, Josien C.
NODeJ: an ImageJ plugin for 3D segmentation of nuclear objects.
- DOI:10.1186/s12859-022-04743-6
- 发表时间:2022-06-06
- 期刊:
- 影响因子:3
- 作者:Dubos, Tristan;Poulet, Axel;Thomson, Geoffrey;Pery, Emilie;Chausse, Frederic;Tatout, Christophe;Desset, Sophie;van Wolfswinkel, Josien C.;Jacob, Yannick
- 通讯作者:Jacob, Yannick
MtING2 encodes an ING domain PHD finger protein which affects Medicago growth, flowering, global patterns of H3K4me3, and gene expression.
- DOI:10.1111/tpj.15994
- 发表时间:2022-11
- 期刊:
- 影响因子:7.2
- 作者:Jaudal, Mauren;Mayo-Smith, Matthew;Poulet, Axel;Whibley, Annabel;Peng, Yongyan;Zhang, Lulu;Thomson, Geoffrey;Trimborn, Laura;Jacob, Yannick;van Wolfswinkel, Josien C.;Goldstone, David C.;Wen, Jiangqi;Mysore, Kirankumar S.;Putterill, Joanna
- 通讯作者:Putterill, Joanna
{{
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 }}
Josephina C van Wolfswinkel其他文献
Josephina C van Wolfswinkel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('Josephina C van Wolfswinkel', 18)}}的其他基金
Role of transposon regulation in the negligible senescence of S. mediterranea
转座子调控在地中海链霉菌可忽略的衰老中的作用
- 批准号:
10518521 - 财政年份:2022
- 资助金额:
$ 41.33万 - 项目类别:
Role of transposon regulation in the negligible senescence of S. mediterranea
转座子调控在地中海链霉菌可忽略的衰老中的作用
- 批准号:
10665794 - 财政年份:2022
- 资助金额:
$ 41.33万 - 项目类别:
相似国自然基金
成人免疫性血小板减少症(ITP)中血小板因子4(PF4)通过调节CD4+T淋巴细胞糖酵解水平影响Th17/Treg平衡的病理机制研究
- 批准号:82370133
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
依恋相关情景模拟对成人依恋安全感的影响及机制
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
生活方式及遗传背景对成人不同生命阶段寿命及死亡的影响及机制的队列研究
- 批准号:
- 批准年份:2021
- 资助金额:56 万元
- 项目类别:面上项目
成人与儿童结核病发展的综合研究:细菌菌株和周围微生物组的影响
- 批准号:81961138012
- 批准年份:2019
- 资助金额:100 万元
- 项目类别:国际(地区)合作与交流项目
统计学习影响成人汉语二语学习的认知神经机制
- 批准号:31900778
- 批准年份:2019
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Uncovering Mechanisms of Racial Inequalities in ADRD: Psychosocial Risk and Resilience Factors for White Matter Integrity
揭示 ADRD 中种族不平等的机制:心理社会风险和白质完整性的弹性因素
- 批准号:
10676358 - 财政年份:2024
- 资助金额:
$ 41.33万 - 项目类别:
Climate Change Effects on Pregnancy via a Traditional Food
气候变化通过传统食物对怀孕的影响
- 批准号:
10822202 - 财政年份:2024
- 资助金额:
$ 41.33万 - 项目类别:
A HUMAN IPSC-BASED ORGANOID PLATFORM FOR STUDYING MATERNAL HYPERGLYCEMIA-INDUCED CONGENITAL HEART DEFECTS
基于人体 IPSC 的类器官平台,用于研究母亲高血糖引起的先天性心脏缺陷
- 批准号:
10752276 - 财政年份:2024
- 资助金额:
$ 41.33万 - 项目类别:
The Proactive and Reactive Neuromechanics of Instability in Aging and Dementia with Lewy Bodies
衰老和路易体痴呆中不稳定的主动和反应神经力学
- 批准号:
10749539 - 财政年份:2024
- 资助金额:
$ 41.33万 - 项目类别:
Iron deficits and their relationship with symptoms and cognition in Psychotic Spectrum Disorders
铁缺乏及其与精神病谱系障碍症状和认知的关系
- 批准号:
10595270 - 财政年份:2023
- 资助金额:
$ 41.33万 - 项目类别: