Diversity in a Dish: Pluripotent Stem Cells in Genetic Analysis and Disease Modeling

项目总结 多能干细胞的研究和实验应用迅速扩大，这些细胞现在提供了 人类疾病和个性化再生医学的重要研究模式。然而，大多数人 到目前为止，利用干细胞的研究使用的是遗传受限的小鼠细胞或克隆人细胞 很少注意细胞遗传多样性对表型和功能结果的影响的品系 以及它与人类多样性的关联性。重要的是，来自小鼠和人类多能干细胞研究的最新数据 细胞表明，遗传变异是分子和细胞差异的最重要驱动因素。 表型，包括建立多能细胞系的容易程度，自发分化率， 将分化的细胞重新编程为多能状态，以及未来干细胞的个性化使用 治疗学。因此，现在有一种未得到满足的需要，在当前的会议上没有得到严格的解决，以了解 基因变异对干细胞生物学的后果及其对发育的影响。为了填补这一空白，我们 建议召开独特而及时的会议《碟子中的多样性：遗传分析和多潜能干细胞研究》 “疾病建模”，以促进小鼠和 人类遗传学、细胞生物学和多能性，并吸引不同的学习者作为下一代 干细胞研究人员。我们提议于2023年在杰克逊酒店举行为期3天的年度密集会议。 位于缅因州巴尔港的实验室。我们将汇集50名科学家，跨越职业生涯阶段，来自以下领域 遗传学、细胞生物学和多能性，以及为那些无法或 选择不亲自出席。对于目标1，我们将召开一次跨学科研讨会，围绕 尖端的研究研讨会和研讨会，重点关注技术技能的获得以及严密性和重复性 应用于干细胞研究和基因组分析。在目标2中，我们将促进互动性和包容性 活动，以促进网络、指导、学习者参与、协作研究和职业生涯 发展。这些活动包括实习生演讲和简短的演讲，以及集中在晚上的讨论。 关于研究项目，严谨和道德，以及英勇无畏。这些目标是由住宅促进的 日本宇宙航空研究开发机构公海会议中心的性质。在目标3中，我们将促进招聘工作的多样性 参与者和正在生成的研究人类疾病模型的工具中。不同的与会者将会是 积极招聘，将提供奖学金，以实现亲自出席，并提供包容性的虚拟选项 将使那些无法旅行的人能够参与。还将在以下背景下强调多样性 研究的最佳做法，包括研究遗传多样性干细胞小组的必要性，以及公平 从更广泛的背景代表中获取、表示和分布细胞系，以确保 从这些生物医学资源中发现的利益是公平分享的。

PROJECT SUMMARY Research and experimental use of pluripotent stem cells has expanded rapidly, and these cells now provide important research models of human disease and personalized regenerative medicine. However, the majority of research to date that has utilized stem cells has employed genetically-limited murine cells or clonal human cell lines with little attention paid to the impact of cellular genetic diversity on the phenotypic and functional outcomes and its relevance to human diversity. Importantly, recent data from murine and human studies of pluripotent stem cells indicate that genetic variability is the most significant driver of molecular and cellular differences in phenotype, including the ease of establishment of pluripotent cell lines, the rate of spontaneous differentiation, reprogramming differentiated cells to a pluripotent state, and the future use of stem cells as personalized therapeutics. Thus, there is now an unmet need, not rigorously addressed at current conferences, to understand the consequences of genetic variation on stem cell biology and their impact on development. To fill this gap, we propose the unique and timely conference “Diversity in a Dish: Pluripotent Stem Cells in Genetic Analysis and Disease Modeling” to facilitate interdisciplinary interactions and collaborations between experts in mouse and human genetics, cell biology, and pluripotency, and to engage diverse learners who are the next generation of stem cell researchers. We propose an annual, intensive 3-day conference beginning in 2023 at The Jackson Laboratory in Bar Harbor, ME. We will bring together 50 scientists, spanning career stages, from the fields of genetics, cell biology, and pluripotency, as well as provide a virtual attendance option for those that cannot or choose not to attend in person. For Aim 1, we will convene an interdisciplinary symposium organized around cutting-edge research seminars, workshops that focus on technical skill acquisition, and rigor and reproducibility as applied to stem cell research and genomic analyses. In Aim 2, we will promote interactive and inclusive activities, to promote networking, mentorship, learner involvement, collaborative research, and career development. These activities include trainee presentations and short talks, and evening discussions focused on research projects, rigor and ethics, and grantsmanship. These objectives are facilitated by the residential nature of the JAX Highseas Conference Center. In Aim 3, we will promote diversity in both the recruitment of participants and in the tools being generated to study models of human disease. Diverse attendees will be actively recruited, scholarships will be provided to enable in-person attendance, and an inclusive virtual option will enable participation by those that are unable to travel. Diversity will also be emphasized in the context of best practices for research, including the need for studies of genetically diverse panels of stem cells, and fair acquisition, representation, and distribution of cell lines from wider representation of backgrounds to ensure the benefits discovered from these biomedical resources are shared equitably.