Stretch-activated ion channels in human neural stem cell mechanotransduction

人神经干细胞机械转导中的拉伸激活离子通道

• 批准号: 8893403
• 负责人: Francesco Tombola
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893403
• 关键词: Affect; Alzheimer' s Disease; Astrocytes; Biocompatible Materials; Biophysics; Brain; Cell Culture Techniques; Cell Differentiation process; Cell Fate Control; Cell Transplants; Cell membrane; Cell physiology; Cells; Complex; Cues; Data; Detection; Development; Disease; Drug Targeting; Environment; Event; Exclusion; Future; Genetic; Glass; Goals; Human; In Vitro; Injury; Ion Channel; Lead; Light; Link; Mechanics; Mediating; Memory; Molecular; Neuraxis; Neurons; Nuclear; Oligodendroglia; Outcome; Parkinson Disease; Property; Regenerative Medicine; Role; Signal Transduction; Signaling Molecule; Specific qualifier value; Spinal cord injury; Stem cell transplant; Stem cells; Stimulus; Stretching; Swelling; Testing; Therapeutic; Tissues; Transplantation; base; brain tissue; cell motility; cell type; in vivo; injured; insight; nerve stem cell; neurogenesis; novel; public health relevance; relating to nervous system; repaired; research study; stem; stem cell biology; stem cell differentiation; stem cell fate; transcription factor

 DESCRIPTION (provided by applicant): Mechanical forces powerfully modulate stem cell fate. Despite the emerging importance of these forces in stem cell differentiation, the molecular mechanisms by which mechanical cues direct cell fate remain unknown. We propose that the stretch-activated ion channels (SACs) transduce mechanical information sensed at the plasma membrane to downstream signaling molecules that control cell fate. In this revised application we will test this hypothesis in light of new preliminary data from our group demonstrating that the recently-identified SAC Piezo1 underlies mechanotransduction currents in human neural stem/progenitor cells and influences neuronal-glial lineage choice. In Aim 1 we will directly test the hypothesis that Piezo1 links mechanical signals to downstream transcription factor activity and mechanosensitive lineage specification. In Aim 2 we will determine whether Piezo1 activity is involved in lineage specification in vivo. Together, the two Aims will establish Piezo1 as a ke signaling molecule in mechanoregulation of human neural stem/progenitor cell fate. In summary, this proposal brings together our expertise in ion channel biophysics, mechanics, biomaterials and stem cell biology to uncover a new molecular player with implications for both, basic stem cell biology and future developments in regenerative medicine.