Human Developmental Biology Resource (HDBR): an embryonic and fetal tissue bank for functional genetics and cell-based research

出生缺陷发生在3%的怀孕和负责20%的婴儿死亡。这些疾病包括脊柱裂、心脏穿孔、唇腭裂等疾病，这些疾病往往会给儿童带来终身的医疗问题，给家庭带来照顾方面的挑战，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，但最终目标是了解胚胎和胎儿的出生缺陷是如何发展的，以便提供预防措施。这些可能涉及重要的营养素，如叶酸，或干细胞移植，这对未来的疾病治疗有很大的希望。此外，许多罕见的疾病，无论是儿童和成人首先出现的问题，由于在出生前的胎儿发育过程中。研究人员越来越多地发现与这些疾病有关的缺陷基因，这增加了将来提供遗传咨询和基因治疗的可能性。然而，我们需要了解这些基因在胚胎和胎儿中的功能，以便朝着新的诊断和治疗方法迈进。虽然对动物的研究可以帮助提供关于这些疾病起源的信息，但最终没有其他选择来研究人类本身的过程。人类发育生物学资源（HDBR）通过为科学家提供来自人类胚胎和胎儿的材料来实现这一重要研究。HDBR已获得伦理和人类组织管理局的批准，可以收集、储存和分发人类胎儿材料用于研究。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。检查样本的发育阶段，并测试其染色体以确定它们是否正常。然后，这些组织要么被送到研究人员那里立即制备细胞培养物或生物分子，要么被冷冻或以其他方式保存，以便以后分发给研究人员。样本详细信息记录在一个匿名的安全数据库中，因此数据中不存在与捐赠妇女的链接。在需要时，人类生物资源研究所的工作人员还代表科学家进行人体材料的研究工作。迄今为止，已有400多个不同的研究项目收到了人类生物资源研究所提供的材料，并发表了200多篇科学论文。这些发现包括相互作用导致先天性巨结肠症（肠道神经缺失）的基因，对精神分裂症基因的更好理解，以及对严重眼睛缺陷基因的鉴定。通过这种方式，科学家们正在使用HDBR材料来了解基因如何促进人类发育，以及这些基因中的突变（错误）如何导致出生缺陷或罕见疾病。在本提案中，HDBR寻求进一步的资金，以继续向国际科学界提供服务。新的发展将包括：（一）根据人类大脑发育研究的需要，重点将收集工作扩大到胎儿后期;（二）对因产前诊断出的出生缺陷而终止妊娠的胎儿材料进行新的系统收集，从而能够对这些疾病进行研究;（iii）扩大HDBR向研究人员提供的组织制备物，以包括适合于单细胞遗传学研究的材料，这在技术上已成为可能;（iv）在我们的实验室提供“旅馆”设施，使研究人员能够接受最佳使用HDBR材料的培训;（v）将遗传学研究的数据与我们现有的基因表达数据库建立新的联系人类发展研究网络; HuDSeN），这将首次使科学家能够观察单个基因如何在人类胚胎中表达。胎儿与存在于该组织或发育阶段的所有活性基因和蛋白质的关系。

Birth defects occur in 3% of pregnancies and are responsible for 20% of infant deaths. They include conditions like spina bifida, hole-in-the-heart, and cleft lip and palate which pose often 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.In addition, many rare diseases of both children and adults first arise owing to a problem during development of the fetus before birth. Researchers are increasingly finding faulty genes to be associated with such diseases, raising the possibility that genetic counselling and perhaps gene therapy might be offered in future. However, we need to understand how such genes function in the embryo and fetus, in order to move forward towards new methods of diagnosis and treatment. While research in animals can help in providing information on the origin of such diseases, there is ultimately no alternative to studying the processes in humans themselves. The Human Developmental Biology Resource (HDBR) enables this vital research by providing scientists with access to material from human embryos and fetuses. 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 the pregnancy. The samples are examined for stage of development and their chromosomes are tested to determine if they are normal. The tissues are then either sent to researchers for immediate preparation of cell cultures or 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 in the data. HDBR staff also carry out research work on the human material, on behalf of scientists, where this is required.To date, over 400 different research projects have received material from the HDBR, and this has led to over 200 scientific papers being published. Discoveries have included genes that interact to cause Hirschsprung's disease (absent nerves in the bowel), an improved understanding of genes contributing to schizophrenia and the identification of genes for severe eye defects. In this way, scientists are using HDBR material to learn how genes contribute to human development and how mutations (mistakes) in these genes may lead to birth defects or rare diseases. In the present proposal, the HDBR seeks further funding to pursue and extend its service to the international scientific community. New developments will include: (i) a focus on extending the collection to later fetal stages, as required for studies of human brain development; (ii) a new systematic collection of fetal material from pregnancies being terminated because of prenatally diagnosed birth defects, thereby allowing research into these diseases; (iii) expanding the tissue preparations that HDBR provides to researchers, to include material suitable for studies of the genetics of single cells, which is now becoming technically possible; (iv) the provision of 'hotel' facilities in our laboratories to enable researchers to be trained in best use of HDBR material; (v) a new linkage of data from genetics studies with our existing gene expression database (Human Developmental Studies Network; HuDSeN) which will for the first time allow scientists to observe how individual genes are expressed in the human embryo/fetus in relation to all the active genes and proteins that are present in that tissue or at that stage of development.