Fetal Microchimerism in the Human Brain

描述（由申请人提供）：微嵌合体（Mc）是指从遗传上不同的个体携带少量细胞或DNA。在母亲和孩子的身体结合结束多年后，在母亲体内发现胎儿Mc，在她的后代体内发现母亲Mc。已在儿童和成人的血液和器官（包括心脏、肝脏、脾脏、肾脏和胰腺）中鉴定出胎儿Mc和母体Mc。尽管大脑对人类健康和功能的重要性，但人类大脑中的Mc存在根本的知识差距。最近的实验研究支持了人类大脑可能包含女性中的胎儿Mc和她的后代中的母体Mc，其中在母体小鼠大脑中鉴定出胎儿Mc，在胎儿小鼠大脑中鉴定出母体Mc。此外，在实验和人体研究中，Mc似乎具有分化的能力，例如，在心脏中产生心肌细胞，在胰腺中产生胰岛B细胞，在肝脏中产生肝细胞。本研究将首次鉴定和表征人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患病率，数量和细胞表型将在不同年龄和根据特定的大脑区域确定。为了建立关于母亲Mc的初步信息，将研究来自家庭成员参与的药物难治性癫痫患者的手术切除脑标本。在这些研究中，将通过HLA和其他多态性特异性定量PCR（qPCR）特异性测定母体Mc。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，包括来自年长的兄弟姐妹，由母亲传给随后怀孕的胎儿，或消失的双胞胎。Mc影响人类大脑的方式是多种多样的，既有利于个人，也不利于个人。如果自然获得的Mc是我们假设的生物学的一个基本方面，那么这项工作将为研究人类大脑的各种疾病奠定基础，包括自身免疫性疾病，肿瘤，发育和退行性疾病。 公共卫生相关性：一些细胞在怀孕期间在母亲和胎儿之间双向运输，令人惊讶的是，来自胎儿的少量细胞在母亲体内持续存在，并且从母亲在她的孩子中持续存在，包括进入成年生活。这些细胞可能具有有益和不利的影响。健康的大脑对人类的功能很重要，这项研究将调查这些自然获得的胎儿和母体细胞， 第一次在人脑中。

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.