Mapping the Marmoset: Characterizing the impacts of chimerism on marmoset development and aging

项目摘要 绒猴最近成为一种非常容易驾驭的非人类灵长类动物衰老模型。 绒猴的寿命相对较短，并表现出与人类相似的衰老相关衰退，包括 血压、免疫功能和认知能力的变化。然而，有一个生物“黑匣子”， 绒猴生物学，很少有研究人员提到的影响。绒猴是天然的嵌合体， 在子宫内交换遗传物质的兄弟姐妹。一些报道将嵌合体仅限于造血组织（例如， 血液、脾、骨髓），而其他人认为其他类型的组织也可以是嵌合的，包括 生殖系组织，与遗传性的影响。目前还不清楚多个基因组的存在是如何在 个体影响绒猴生理学和与年龄相关的发病率的风险。本研究的基本原理 为了理解绒猴模型的优点和局限性，我们必须描述 以及嵌合体对个体的影响。这些努力对于实现能够 预测和确定嵌合体的结果。随着越来越多的人认识到人类的嵌合体 嵌合体的绒猴模型既广泛又是人类健康的主要驱动力，可能是研究嵌合体的关键工具。 老化研究因此，本提案的具体目标是：1）定义并绘制绒猴嵌合体，2） 描述绒猴嵌合体的发育动力学特征，3）评估嵌合体的成本， 衰老的绒猴

PROJECT SUMMARY The marmoset monkey has emerged recently as a highly tractable nonhuman primate model of aging. Marmosets have relatively short lifespans, and exhibit similar aging-related declines to humans, including changes in blood pressure, immune function, and cognition. However, there is a biological “black box” in marmoset biology, the implications of which few researchers mention. Marmosets are natural chimeras, with siblings exchanging genetic material in utero. Some reports limit chimerism to only hematopoietic tissues (e.g., blood, spleen, bone marrow) whereas others suggest that other types of tissue can be chimeric, including germline tissues, with implications for heritability. It remains unclear how the presence of multiple genomes in an individual impacts marmoset physiology and the risk of age-related morbidities. The rationale for this study is that to understand the benefits and limitations of the marmoset model we must characterize the emergence and impacts of chimerism on an individual. These efforts are imperative to the overall objective of being able to predict and determine outcomes of chimerism. With the increasing appreciation that chimerism in humans is both widespread and a major driver of human health, marmoset models of chimerism may be a pivotal tool in aging research. Therefore, the specific aims for this proposal to 1) Define and map chimerism in marmosets, 2) Characterize the developmental dynamics of marmoset chimerism, and 3) Evaluate the costs of chimerism for aging marmosets.