Non-coding RNA In Stem Cell Biology

干细胞生物学中的非编码 RNA

• 批准号: 10451518
• 负责人: Josephina C van Wolfswinkel
• 金额: $ 41.33万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10451518
• 关键词: Address; Adult; Affect; Aging; Animals; Binding; Biology; Cell Differentiation process; Cells; Chromatin; Congenital Abnormality; Embryonic Development; Failure; Fertility; Functional disorder; Gene Expression Regulation; Genome Stability; Germ Cells; Goals; In Vitro; Infertility; Malignant Neoplasms; Mediating; Molecular; Natural regeneration; Outcome; Pathway interactions; Planarians; Pluripotent Stem Cells; Population; Process; Proteins; RNA; Regulation; Role; Small RNA; Therapeutic; Untranslated RNA; in vivo; insight; pluripotency; stem cell biology; stem cell function; stem cells; targeted treatment

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.

项目总结

项目成果

The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum.

• DOI: 10.3390/ijms24021051
• 发表时间: 2023-01-05
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 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: Cell reports
• 影响因子: 8.8
• 作者: Li D;Taylor DH;van Wolfswinkel JC
• 通讯作者: van Wolfswinkel JC

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: PLANT JOURNAL
• 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

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: SCIENCE ADVANCES
• 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: BMC BIOINFORMATICS
• 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