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Fetal Microchimerism in the Human Brain

人脑中的胎儿微嵌合现象

基本信息

批准号：
8302683
负责人：
J. Lee Nelson
金额：
$ 27.81万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-01 至 2014-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): 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 fo 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. PUBLIC HEALTH RELEVANCE: Some cells traffic in both directions between a mother and fetus during pregnancy and surprisingly, small numbers of cells from the fetus persist in the mother, and from the mother in her children, including into adult life. These cells are likely to have both beneficial and adverse effects. A healthy brain is important to human functioning and studies in this proposal will investigate these naturally acquired fetal and maternal cells for the first time in the human brain.

描述(申请人提供)：微嵌合体(Mc)指的是含有少量来自不同基因个体的细胞或DNA。在母子身体结合结束许多年后，母亲体内发现了胎儿的Mc，她的后代中发现了母体的Mc。在儿童和成人的血液和包括心脏、肝脏、脾、肾和胰腺在内的器官中都发现了胎儿Mc和母体Mc。尽管大脑对人类的健康和功能很重要，但人类大脑中对Mc的认识存在一个根本的缺口。最近的实验研究支持人类大脑中可能含有女性的胎儿Mc和子代的母体Mc，其中在母鼠脑中发现了胎儿Mc，在胎鼠脑中发现了母体Mc。此外，在实验和人体研究中，Mc似乎具有分化能力，例如在心脏产生心肌细胞，在胰腺产生胰岛b细胞，在肝脏产生肝细胞。这项提议中的研究将首次识别和表征人类大脑中自然获得的胎儿Mc和母体Mc。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不同年龄和特定脑区进行确定。为了确定母体Mc的初步信息，将研究家庭成员参与的药物难治性癫痫患者的手术切除的脑组织样本。在这些研究中，母亲的Mc将通过人类白细胞抗原和其他多态特异性定量聚合酶链式反应(QPCR)进行特异性检测。所有家庭成员的参与将允许进一步评估其他潜在的Mc来源，包括来自较年长的兄弟姐妹，由母亲传递给下一次怀孕的胎儿，或消失的双胞胎。Mc影响人类大脑的方式是多种多样的，对个人既有好处，也有坏处。如果像我们假设的那样，自然获得的Mc是生物学的一个基本方面，那么拟议的工作将创造一个基础，可以从这个基础上研究人类大脑的各种疾病，包括自身免疫、肿瘤、发育和退行性疾病。公共卫生相关性：在怀孕期间，一些细胞在母亲和胎儿之间双向流动，令人惊讶的是，来自胎儿的少量细胞在母亲体内存活，来自母亲的细胞在她的孩子中存活，包括进入成年生活。这些细胞可能既有有益的影响，也有不利的影响。一个健康的大脑对人类的功能很重要，这项建议中的研究将研究这些自然获得的胎儿和母体细胞这在人类大脑中是第一次。