Neuronal regulation of salivary stem cells

唾液干细胞的神经调节

• 批准号: 9404873
• 负责人: Sarah Monica Knox
• 金额: $ 39.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9404873
• 关键词: Acetylcholine; Acinar Cell; Acinus organ component; Adult; Aftercare; Autologous; Behavior; Biochemical; Cell Differentiation process; Cell Proliferation; Cell Transplants; Cells; Data; Disease; Duct (organ) structure; Embryonic Development; Epithelial; Event; Fetal Tissues; Functional disorder; Genetic; Gland; Goals; Head and Neck Cancer; Homeostasis; Human; Imaging Techniques; Injury; Knowledge; Maintenance; Malignant Neoplasms; Modeling; Mus; Natural regeneration; Nerve; Neuregulin 1; Neurons; Operative Surgical Procedures; Oral health; Organ; Pathologic; Patients; Population; Quality of life; Radiation; Radiation therapy; Regulation; Reporting; Salivary; Salivary Glands; Signal Pathway; Signal Transduction; Stem cell transplant; Stem cells; Structure; Surface Antigens; System; Testing; Therapeutic; Tissues; base; bench to bedside; cell type; design; experimental study; fetal; fluorescence imaging; gland development; injured; innovation; irradiation; keratin 5; nerve supply; neurotransmission; novel therapeutic intervention; progenitor; public health relevance; regenerative; repaired; response; self-renewal; stem; stem cell therapy; tissue regeneration; tissue repair

DESCRIPTION (provided by applicant): Salivary gland dysfunction occurs as a result of pathological injury after radiotherapy for head and neck cancer and significantly compromises the oral health and quality of life of patients. A potential regenerative approach for restoring salivary function is stem cell therapy, where autologous stem/progenitor cells are transplanted into the injured organ or stem cells within the tissue are reactivated. However, the identity of human stem/progenitors and how they are regulated are unknown. In this application we propose to determine the contributions of putative progenitors in the mouse and human salivary gland to tissue repair and regeneration and to determine the influence of neuronal signals on their behavior. Parasympathetic nerves are essential to salivary function and regeneration, as well as the maintenance of epithelial progenitor cells, and are severely reduced in human salivary glands after radiotherapy. We hypothesize that discrete epithelial progenitor cells in the adult mouse and human salivary gland regenerate acini during homeostasis and injury in response to neuronal signals. Thus, the Specific Aims of this project are to: 1) Define the mechanisms by which parasympathetic nerves regulate progenitor cell fate, 2) Determine the contribution of salivary progenitor cells and neuronal signaling to adult homeostasis and repair and 3) Identify epithelial progenitor cells in the human salivary gland. These aims will be achieved using a combination of human salivary glands and mouse genetics in conjunction with genetic, biochemical, immunochemical, and fluorescence imaging techniques. Our rationale for investigating this hypothesis is that understanding progenitor cell identity in the salivary gland and the mechanisms that regulate salivary tissue regeneration will enable the design of targeted regenerative approaches to reverse salivary dysfunction.

描述（由申请人提供）：唾液腺功能障碍是由于放射疗法治疗头颈癌后病理损伤而导致的，并显着损害了患者的口腔健康和生活质量。恢复唾液功能的潜在再生方法是干细胞疗法，其中自体茎/祖细胞被移植到组织内的受伤器官或干细胞中。但是，人类/祖细胞的身份及其如何受到调节。在此应用中，我们建议确定小鼠和人类唾液腺中假定祖细胞对组织修复和再生的贡献，并确定神经元信号对其行为的影响。副交感神经对于唾液功能和再生以及上皮祖细胞的维持至关重要，放疗后人类唾液腺中严重降低。我们假设该离散的上皮祖细胞 成年小鼠和人类唾液腺在体内平衡期间再生肌动症，并响应神经元信号而受伤。因此，该项目的具体目的是：1）定义副交感神经调节祖细胞命运的机制，2）确定唾液祖细胞和神经信号对成人稳态和修复的贡献，以及3）识别人类溶性腺中上皮祖细胞。这些目标将通过人类唾液腺和小鼠遗传学与遗传，生化，免疫化学和荧光成像技术结合结合来实现。我们研究这一假设的理由是，了解唾液腺中的祖细胞身份以及调节唾液组织再生的机制将使靶向再生方法的设计逆转唾液功能障碍。

项目成果

Salivary gland stem cells: A review of development, regeneration and cancer.

• DOI: 10.1002/dvg.23211
• 发表时间: 2018-05
• 期刊: Genesis (New York, N.Y. : 2000)
• 作者: Emmerson E;Knox SM
• 通讯作者: Knox SM

Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling.

• DOI: 10.1016/j.devcel.2022.10.011
• 发表时间: 2022-11-21
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: May, Alison J.;Mattingly, Aaron J.;Gaylord, Eliza A.;Griffin, Nathan;Sudiwala, Sonia;Cruz-Pacheco, Noel;Emmerson, Elaine;Mohabbat, Seayar;Nathan, Sara;Sinada, Hanan;Lombaert, Isabelle M. A.;Knox, Sarah M.
• 通讯作者: Knox, Sarah M.

CD29 is highly expressed on epithelial, myoepithelial, and mesenchymal stromal cells of human salivary glands.

CD29 在人唾液腺的上皮细胞、肌上皮细胞和间充质基质细胞上高表达。

• DOI: 10.1111/odi.12812
• 发表时间: 2018
• 期刊: Oral diseases
• 影响因子: 3.8
• 作者: Togarrati,PP;Dinglasan,N;Desai,S;Ryan,WR;Muench,MO
• 通讯作者: Muench,MO