Fetal Microchimerism in the Human Brain

人脑中的胎儿微嵌合现象

• 批准号: 8413044
• 负责人: J. Lee Nelson
• 金额: $ 20.76万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8413044
• 关键词: Adult; Adverse effects; Affect; Age; Autoimmune Process; Autopsy; Biological Assay; Biology; Blood; Brain; Brain region; Cardiac Myocytes; Cell Count; Cells; Child; DNA; Degenerative Disorder; Development; Disease; Effector Cell; Epilepsy; Evaluation; Family member; Female; Fetus; Foundations; Genetic Polymorphism; Health; Heart; Hepatocyte; Human; Immune; Immune Targeting; Immunologic Surveillance; Individual; Kidney; Knowledge; Life; Liver; Location; Microchimerism; Mothers; Mus; Organ; Pancreas; Patients; Pharmaceutical Preparations; Phenotype; Pregnancy; Prevalence; Refractory; Siblings; Source; Specimen; Spleen; Time; Twin Multiple Birth; Woman; Work; fetal; fetus cell; human disease; human female; islet; male; neoplastic; research study; tissue repair; trafficking; tumor

PROJECT SUMMARY/ABSTRACT Microchimerism (Mc) refers to harboring a small amount of cells or DNA from a genetically distinct individual. Many years after the physical union of mother and child ends fetal Mc is found in the mother and maternal Mc is found in her progeny. Fetal Mc and maternal Mc have been identified in children and adults, in blood and organs including heart, liver, spleen, kidney and pancreas. Despite the importance of the brain to human health and function a fundamental gap in knowledge exists for Mc in the human brain. That human brain is likely to contain fetal Mc in women and maternal Mc in her progeny is supported by recent experimental studies in which fetal Mc was identified in the maternal mouse brain and maternal Mc in the fetal mouse brain. Moreover, in experimental and human studies Mc appears to have the capacity to differentiate creating, for example, cardiac myocytes in the heart, islet b cells in the pancreas and hepatocytes in the liver. Studies in this proposal will for the first time identify and characterize naturally acquired fetal Mc and maternal Mc in the human brain. To establish fundamental initial knowledge fetal Mc prevalence, quantity and cell phenotypes will be determined across age and according to specific brain regions. To establish initial information about maternal Mc surgically excised brain specimens will be studied from patients with medication refractory epilepsy for whom family members participate. In these studies maternal Mc will be specifically assayed by HLA and other polymorphism specific quantitative PCR (qPCR). Participation of all family members will permit further evaluation for other potential Mc sources including from an older sibling, passed by the mother to the fetus of a subsequent pregnancy, or a vanished twin. The ways in which Mc could affect the human brain are multiple and diverse, both to the benefit and detriment of the individual. If naturally acquired Mc is a basic aspect of biology as we hypothesize, the proposed work will have created a foundation from which diverse disorders of the human brain can be investigated, including autoimmune, neoplastic, developmental and degenerative conditions.

项目总结/摘要 微嵌合体（Microchimerism，Mc）是指从遗传上不同的个体中携带少量细胞或DNA。 在母亲和孩子的身体结合结束多年后，在母亲和母亲的Mc中发现了胎儿Mc 在她的后代身上已在儿童和成人、血液和血液中鉴定出胎儿Mc和母体Mc。 器官包括心脏、肝脏、脾脏、肾脏和胰腺。尽管大脑对人类的重要性 健康和功能对于人类大脑中的Mc存在根本的知识缺口。人类的大脑 最近的实验结果支持了在女性中可能含有胎儿Mc并且在她的后代中含有母体Mc的说法。 在母体小鼠脑中鉴定出胎儿Mc和在胎儿小鼠脑中鉴定出母体Mc的研究。 此外，在实验和人体研究中，Mc似乎有能力区分创造，因为 例如，心脏中的心肌细胞、胰腺中的胰岛B细胞和肝脏中的肝细胞。研究 这一建议将首次确定和表征自然获得的胎儿Mc和母体Mc， 人脑为了建立基本的初步知识，胎儿Mc的患病率，数量和细胞表型将 根据年龄和特定的大脑区域来确定。建立有关的初始信息 将研究来自药物难治性患者的母体Mc手术切除的脑标本。 癫痫病患者家属参加。在这些研究中，将通过以下方法特异性测定母体Mc： HLA和其他多态性特异性定量PCR（qPCR）。所有家庭成员均可参加 进一步评估其他潜在的Mc来源，包括来自年长的兄弟姐妹，由母亲传给 后续怀孕的胎儿或者消失的双胞胎Mc影响人类大脑的方式有 多样性和多样性，既有利于个人，也不利于个人。如果自然获得的Mc是一个基本的 生物学方面，因为我们假设，拟议的工作将创造一个基础，从不同的 可以研究人脑的疾病，包括自身免疫性、肿瘤性、发育性和 退化的条件。