Doctoral Dissertation Research: Evolutionary Perspectives on Microchimerism

除了传统的基因遗传，母亲还可以通过传递免疫因子、表观遗传标记和有益微生物来影响后代的生物学。另一种不太为人所知的非传统遗传模式被称为微嵌合，细胞在怀孕期间在母亲和婴儿之间移动，有些细胞在出生后定居并持续数十年。本博士论文项目利用来自多代纵向健康和营养研究的数据，调查微嵌合在整个生命过程中作为免疫权衡的中介因素。该研究旨在更好地了解微嵌合如何与妊娠期间胎儿生长、婴儿喂养方式、幼儿传染病和成人妊娠结局相关。这项纵向研究的公开数据和新产生的微嵌合数据将为本科生（包括来自代表性不足群体的个人）提供学生驱动的研究机会。微嵌合被认为通过直接贡献干细胞分化并发育成功能性免疫细胞和表达触发宿主免疫反应的外源抗原来影响宿主免疫功能。大多数微嵌合研究都集中在与自身免疫性疾病、癌症、移植生物学和不良妊娠结局的关系上，在理解为什么有些个体比其他人更容易被微嵌合细胞定植，以及这些差异如何影响进化适应性方面留下了相当大的空白。为了澄清这些问题，宿务纵向健康和营养调查的人口数据涵盖了三代参与者，将用于调查以下具体目标：1)评估婴儿期母乳喂养是否能预测成年期的微嵌合现象，2)评估微嵌合现象是否与较低的早期感染风险相关，3)确定从母亲那里获得微嵌合的成年妇女是否有较低的不良妊娠结局风险，因为她们有自己的后代。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Beyond conventional genetic inheritance, mothers can impact their offspring's biology through the transfer of immune factors, epigenetic markers, and beneficial microbes. Another lesser-known, non-conventional mode of inheritance is called microchimerism, whereby cells travel between mother and baby during pregnancy, and some colonize and persist for decades after birth. This doctoral dissertation project leverages data from a multigenerational, longitudinal health and nutrition study to investigate microchimerism as a mediating factor in immune tradeoffs throughout the life course. The research aims to better understand how microchimerism may be associated with fetal growth during pregnancy, infant feeding practices, early childhood infectious disease, and pregnancy outcomes in adults. The publicly available data from this longitudinal study and the newly-generated microchimerism data will provide opportunities for student-driven research for undergraduates, including individuals from underrepresented groups.Microchimerism is thought to influence host immune function by directly contributing stem cells that differentiate and develop into functional immune cells and expressing foreign antigens that trigger host immune responses. Most microchimerism research has focused on relationships with autoimmune disorders, cancer, transplant biology, and adverse pregnancy outcomes, leaving considerable gaps in understanding why some individuals are colonized by microchimeric cells more than others, and how these differences might impact evolutionary fitness. To clarify these issues, population-based data from the Cebu Longitudinal Health and Nutrition Survey spanning three generations of participants will be used to investigate the following specific aims: 1) evaluate whether having been breastfed in infancy predicts microchimerism in adulthood, 2) assess whether microchimerism is associated with lower risk of early life infection, and 3) determine whether adult women with microchimerism from their mothers have lower risk of adverse pregnancy outcomes as they have offspring of their own.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.