Comparative systems biology defines regulatory mechanisms in whole-body regeneration

比较系统生物学定义全身再生的调节机制

• 批准号: 10656329
• 负责人: Bo Wang
• 金额: $ 39.33万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656329
• 关键词: ATAC-seq; Animals; Biological; Biology; Body part; Cell Proliferation; Cells; Chimera organism; Coupled; Fresh Water; Genes; Growth; Human; Immunologics; Knowledge; Medical; Natural regeneration; Operative Surgical Procedures; Pathogenicity; Pathway interactions; Patients; Planarians; Platyhelminths; Process; Regenerative Medicine; Risk; Schistosoma; Systems Biology; Therapeutic; Tissues; Traumatic injury; comparative; experimental study; functional genomics; network dysfunction; programs; regenerative; response; tissue regeneration; tool; transcriptomics; wound

Project Summary Whole-body regeneration (the ability to regenerate all body parts) is one of the greatest mysteries in biology. Harnessing this process would be a medical moonshot triumph, as it would provide therapeutic strategies to enable regrowth of any type of missing tissues in human patients. In order to understand and control regeneration, we need to uncover the full regulatory network of the regeneration program, and identify critical mechanisms that may lead to the dysfunction of this network. Here, we propose to use new functional genomic analysis tools (Spatial Transcriptomics, ATAC-seq, and single-cell transcriptomics) coupled with high- throughput gene perturbation experiments to study two unique experimental paradigms. In the first paradigm, we will compare two evolutionary cousins: the freshwater planarian, which is an immortal flatworm with unparalleled regenerative ability throughout the animal kingdom, and the pathogenic flatworm schistosome, which only has limited regenerative ability. We will reveal the critical regulatory components of the short-term wound-induced response that are essential for launching and sustaining regeneration. In the second paradigm, we will study surgically constructed planarian chimeras to unravel the immunological pathways that regulate regeneration in order to manage the long-term risks of uncontrolled cell proliferation that is associated with repeated regeneration. Collectively, our study will advance the understanding of the fundamental biological basis of regenerative medicine and provide useful targets for activating regeneration.

项目摘要 全身再生（重生所有身体部位的能力）是生物学中最大的奥秘之一。 利用这一过程将是医学冠军的胜利，因为它将提供治疗策略 在人类患者中启用任何类型的缺失组织的再生。为了理解和控制 再生，我们需要揭示再生计划的完整监管网络，并确定关键 可能导致该网络功能障碍的机制。在这里，我们建议使用新的功能基因组 分析工具（空间转录组学，ATAC-SEQ和单细胞转录组学）与高 - 吞吐基因扰动实验研究了两个独特的实验范例。在第一个范式中， 我们将比较两个进化表亲： 整个动物王国的无与伦比的再生能力，以及致病性的扁虫斑点， 仅具有有限的再生能力。我们将揭示短期的关键监管组成部分 伤口引起的反应对于发射和维持再生至关重要。在第二个范式中， 我们将研究手术构造的扁平嵌合体，以解开调节的免疫途径 为了管理与不受控制的细胞增殖的长期风险 重复再生。总的来说，我们的研究将提高对基本生物学的理解 再生医学的基础，并为激活再生提供了有用的靶标。

项目成果

Cellular diversity and developmental hierarchy in the planarian nervous system.

• DOI: 10.1016/j.gde.2022.101960
• 发表时间: 2022-10
• 期刊: CURRENT OPINION IN GENETICS & DEVELOPMENT
• 影响因子: 4
• 作者: Wyss, Livia S.;Bray, Samuel R.;Wang, Bo
• 通讯作者: Wang, Bo

Single-cell deconstruction of stem-cell-driven schistosome development.

• DOI: 10.1016/j.pt.2021.03.005
• 发表时间: 2021-09
• 期刊: Trends in parasitology
• 影响因子: 9.6
• 作者: Nanes Sarfati D;Li P;Tarashansky AJ;Wang B
• 通讯作者: Wang B

Ultrafast and long-range coordination of wound responses is essential for whole-body regeneration.

伤口反应的超快和远距离协调对于全身再生至关重要。

• DOI: 10.1101/2023.03.15.532844
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Fan,Yuhang;Chai,Chew;Li,Pengyang;Zou,Xinzhi;FerrellJr,JamesE;Wang,Bo
• 通讯作者: Wang,Bo

Mapping single-cell atlases throughout Metazoa unravels cell type evolution.

• DOI: 10.7554/elife.66747
• 发表时间: 2021-05-04
• 期刊: eLife
• 影响因子: 7.7
• 作者: Tarashansky AJ;Musser JM;Khariton M;Li P;Arendt D;Quake SR;Wang B
• 通讯作者: Wang B

Expansion spatial transcriptomics.

扩展空间转录组学。

• DOI: 10.1038/s41592-023-01911-1
• 发表时间: 2023
• 期刊: Nature methods
• 影响因子: 48
• 作者: Fan,Yuhang;Andrusivová,Žaneta;Wu,Yunming;Chai,Chew;Larsson,Ludvig;He,Mengxiao;Luo,Liqun;Lundeberg,Joakim;Wang,Bo
• 通讯作者: Wang,Bo