Human Developmental Biology Resource (HDBR): meeting new trends and challenges in developmental biobanking

人类发育生物学资源（HDBR）：应对发育生物样本库的新趋势和挑战

• 批准号: MR/X008304/1
• 负责人: Deborah Henderson
• 金额: $ 502.2万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX008304%2F1
• 关键词: Human; Developmental; Biology; Resource; HDBR

Understanding how the embryo and fetus develop before birth is important, not only to properly appreciate our origins from the fertilised egg, but also to gain insight into the many diseases that arise before or around the time of birth. Some later childhood or adult diseases also have strong influences from the fetal period. Despite this, we understand rather little about human development and much more about the development of other animals, including the mouse, chicken, fish and even the fruit fly. This poor level of knowledge about human development is now being tackled through studies of tissues from embryos and fetuses, which are obtained after termination of pregnancy. The Human Developmental Biology Resource (HDBR) enables this vital research by providing scientists with access to material from these samples. The HDBR has ethical and Human Tissue Authority approval to collect, store and distribute human fetal material for research. The material is obtained, with informed consent, after the woman has received professional counselling and decided to terminate her pregnancy. The samples are assessed for developmental stage and tested to determine whether they are genetically normal. The tissues are then either immediately sent to researchers to either culture the tissue/cells or to extract the biological molecules, or else the samples are frozen or otherwise preserved for later distribution to researchers. Sample details are recorded on a secure database that is anonymized, so no link to the donating women exists. HDBR also provides a 'research service' where HDBR staff perform research work on the human material on behalf of scientists. To date, over 600 different research projects have received material from the HDBR, and this has led to nearly 400 scientific papers being published.The goals for the next phase of HDBR work are several-fold. We will develop 'research clinics' in which women are invited to complete their pregnancy termination in hospital, rather than at home as is the current health service trend. This will ensure that the HDBR can continue to collect the earliest embryonic stages, which are vital for understanding how organs are first formed. We will also extend tissue collection into the later fetal and newborn periods, where research is urgently needed but samples are rarely available. We will work with scientists to ensure that even the smallest and most hard-to-access parts of the fetus are provided for research. We will extend our collection of abnormal samples, for example from pregnancies that are terminated because of Down Syndrome, or other serious fetal problems. We will establish a new part of the HDBR research service, called Spatial Transcriptomics, in which the expression of genes can be studied directly in the fetal tissues. We will also expand the HDBR Atlas, a publicly available web site where information can be obtained about human development.The eventual aim of this research into human development is to better understand birth defects which occur in 3% of pregnancies and are responsible for 20% of infant deaths. This includes conditions like spina bifida, hole-in-the-heart, and cleft lip and palate which often pose life-long medical problems for the child, caring challenges for the family, and a considerable financial burden for the health service. While pregnancy termination can be an option, the ultimate goal is to learn how birth defects develop in the embryo and fetus, so that preventive measures can be offered. These might involve vital nutrients like folic acid, or stem cell transplants which hold great promise for future disease treatment. Researchers are increasingly finding disruptions of genes that are associated with such diseases, raising the possibility that genetic counselling and perhaps gene therapy might be offered in future. All of these medical advances will be made more achievable by an improved understanding of how the human embryo and fetus develop.

了解胚胎和胎儿在出生前是如何发育的是很重要的，这不仅是为了正确认识我们来自受精卵的起源，也是为了洞察出生之前或出生前后出现的许多疾病。儿童后期或成人的一些疾病也会受到胎儿期的强烈影响。尽管如此，我们对人类的发育了解很少，对其他动物的发育了解更多，包括老鼠、鸡、鱼，甚至果蝇。目前正在通过对终止妊娠后获得的胚胎和胎儿组织的研究来解决有关人类发育的知识水平低下的问题。人类发育生物学资源(HDBR)为科学家提供了从这些样本中获取材料的途径，从而使这项至关重要的研究成为可能。HDBR拥有伦理和人体组织管理局的批准，可以收集、存储和分发用于研究的人类胎儿材料。在妇女接受专业咨询并决定终止妊娠后，在知情同意的情况下获得材料。这些样本被评估为发育阶段，并进行测试，以确定它们是否在遗传上正常。然后，这些组织要么立即被送往研究人员，要么培养组织/细胞，要么提取生物分子，或者将样本冷冻或以其他方式保存，以便稍后分发给研究人员。样本细节被记录在一个匿名的安全数据库中，因此不存在与捐赠者的链接。HDBR还提供“研究服务”，HDBR的工作人员代表科学家对人类材料进行研究。到目前为止，已有600多个不同的研究项目收到了HDBR的材料，这导致了近400篇科学论文的发表。HDBR下一阶段的工作目标是多方面的。我们将发展“研究诊所”，邀请妇女在医院完成终止妊娠，而不是像目前的卫生服务趋势那样在家里完成。这将确保HDBR能够继续收集最早的胚胎阶段，这对于了解器官最初是如何形成的至关重要。我们还将把组织收集扩大到胎儿和新生儿的晚期，这些时期迫切需要研究，但样本很少。我们将与科学家合作，确保即使是胎儿最小、最难接近的部分也能提供给研究。我们将扩大对异常样本的收集，例如，因唐氏综合症或其他严重胎儿问题而终止妊娠的样本。我们将建立HDBR研究服务的一个新部分，称为空间转录组学，其中可以直接在胎儿组织中研究基因的表达。我们还将扩大HDBR地图集，这是一个公开的网站，可以获得有关人类发育的信息。这项人类发育研究的最终目的是更好地了解出生缺陷，这些缺陷发生在3%的怀孕中，并导致20%的婴儿死亡。这包括脊柱裂、心脏穿孔和唇腭裂等疾病，这些疾病往往会给孩子带来终身的医疗问题，对家庭的照顾构成挑战，并给卫生服务带来相当大的经济负担。虽然终止妊娠可以是一种选择，但最终目标是了解出生缺陷在胚胎和胎儿中是如何发展的，以便提供预防措施。这些可能涉及叶酸等重要营养物质，或者干细胞移植，这对未来的疾病治疗具有很大的希望。研究人员越来越多地发现与此类疾病相关的基因中断，这增加了未来可能提供遗传咨询或基因治疗的可能性。通过更好地了解人类胚胎和胎儿是如何发育的，所有这些医学进步都将更加容易实现。