Human Developmental Biology Resource: support for Human Cell Atlas

出生缺陷，如脊柱裂或心脏穿孔，每30个孕妇中就有一个会受到影响，当胎儿出生前发育出现问题时就会出现这种缺陷。即使是年龄较大的儿童或成人的疾病也可能在出生前就有其起源。研究人员越来越多地发现有缺陷的基因与这些疾病有关，这增加了未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，以便找到新的诊断和治疗方法。虽然对动物进行研究可以帮助提供有关这类疾病起源的信息，但最终除了研究人类自身的过程之外，没有其他选择。人类发育生物学资源（HDBR）通过向科学家提供人类胚胎和胎儿的材料，使这项研究成为可能。HDBR已获得伦理委员会和人类组织管理局的批准，可以收集、储存和分发用于研究的人类胎儿材料。材料是在母亲知情同意的情况下，从正在终止的意外怀孕中获得的。HDBR的工作人员检查胎儿样本的发育阶段，并测试其染色体以检测任何异常。然后，这些组织要么被送到研究人员那里立即进行研究，要么将样本冷冻或以其他方式保存起来，以便以后分发给研究人员。样本的详细信息被记录在一个匿名的安全数据库中，因此研究结果不能与捐赠妇女联系起来。迄今为止，已有400多个不同的研究项目收到了来自HDBR的胎儿材料，这导致240多篇科学论文发表。这些发现包括肠道疾病、精神分裂症和严重视力缺陷的基因。通过这种方式，科学家们正在利用HDBR材料来了解基因如何促进人类发育，以及这些基因的突变（错误）如何可能导致出生缺陷或罕见疾病。最近，MRC为一项新的计划拨款：人类细胞图谱（HCA）。在这项研究中，人类胚胎和胎儿的不同器官和组织中活跃的基因将被识别，从而可以识别器官内所有不同类型的细胞。胎儿和成人器官的异同将被特别研究。这一信息将为今后关于基因如何导致出生缺陷和儿童疾病的研究奠定宝贵的基础。HDBR将是这项研究人类胎儿材料的主要提供者，目前的申请寻求额外的资金来支付额外的HDBR工作，这将需要支持这一HCA倡议。HCA倡议中的新研究项目对HDBR及其组织供应链构成了相当大的挑战。因此，HDBR要求额外的资金来支付额外的工作人员和运行费用，以便提供比目前更大规模的服务。HDBR将增加其在堕胎诊所的出勤率，以便收集更多的胎儿样本用于研究。工作人员将接受新的专业组织处理程序的培训，以满足HCA研究的严格要求。提高HDBR的工作效率，确保每一个有价值的胎儿样本都得到尽可能好的利用。将强调与HCA研究小组的密切合作，以确保组织供应与项目需求相协调。最后，将探索使用储存的冷冻组织作为新鲜样本的替代品，因为冷冻组织比新鲜组织更容易供应。在这些方面，HDBR将满足新的HCA项目的需求，并将继续提供最高标准的组织，以实现尽可能高质量的研究。

Birth defects such as spina bifida or hole-in-the-heart affect one in every thirty pregnancies and arise when there is a problem in development of the fetus before birth. Even diseases of older children or adults can have their origins 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 with 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 research by providing scientists with access to material from human embryos and fetuses. The HDBR has approval from an Ethics Committee and from the Human Tissue Authority to collect, store and distribute human fetal material for research. The material is obtained, with informed consent of the mother, from unwanted pregnancies that are being terminated. Staff in the HDBR examine the fetal samples for stage of development and their chromosomes are tested to detect any abnormalities. The tissues are then either sent to researchers for immediate research, 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 results from the research can be linked back to the donating woman. To date, over 400 different research projects have received fetal material from the HDBR, and this has led to over 240 scientific papers being published. Discoveries have included genes for bowel disorders, schizophrenia and 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. Recently, the MRC allocated funds to pay for a new initiative: the Human Cell Atlas (HCA). In this research, the genes that are active in different organs and tissues of the human embryo and fetus will be identified, so that all the different types of cells within the organs can be recognized. Similarities and differences between fetal and adult organs will be especially studied. This information will be valuable in forming a basis for future research on how genes lead to birth defects and children's diseases. The HDBR will be the primary provider of human fetal material for this research, and the present application seeks additional funding to pay for the extra HDBR work that will be needed to support this HCA initiative. The new research projects within the HCA initiative pose considerable challenges for the HDBR and its tissue supply-chain. As a result, the HDBR is requesting extra funding to pay for additional staff members and running costs, in order to deliver a larger-scale service than at present. The HDBR will increase its attendance at abortion clinics, so as to collect extra fetal samples for research. Staff will be trained in new specialist tissue handling procedures that are required for the exacting demands of the HCA research. Operating efficiency of the HDBR will be improved to ensure that every, valuable fetal sample is used as well as possible. Close working with the HCA research teams will be emphasised, to ensure that tissue supply is coordinated with project needs. Finally, the use of stored frozen tissue as an alternative to fresh samples will be explored, as frozen tissue is easier to supply than fresh tissue. In these ways, the HDBR will rise to the demands of the new HCA project and will continue to supply tissues of the highest standards to enable the best possible quality research.