在人源化小鼠中模拟人类胎儿造血。

Modeling Human Fetal Hematopoiesis in Humanized Mice.

机构信息

INSERM U976, Université de Paris, École Pratique des Hautes Études/PSL Research University, Institut de Recherche Saint Louis, Paris, France.

Service d'Hématologie Biologique, Hôpital Tenon, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France.

出版信息

Methods Mol Biol. 2021;2308:225-233. doi: 10.1007/978-1-0716-1425-9_17.

DOI:10.1007/978-1-0716-1425-9_17

PMID:34057726

Abstract

Due to difficulties to access primary human bone marrow samples and age or donor effects, human hematopoiesis has long remained far less well characterized than in the mouse. Despite recent progresses in single-cell RNA profiling only little is known as to phenotype, function and developmental trajectories of human lymphomyeloid progenitors and precursors. This is especially true regarding the developmental architecture of the lymphoid lineage which has been the subject of persistent controversies over the past decades. Here, we describe an original approach of in vivo modeling of human fetal hematopoiesis immunodeficient NSG mice engrafted with neonatal CD34 hematopoietic progenitor cells (HPCs) allowing for rapid identification and isolation of lymphomyeloid developmental intermediates.

摘要

由于难以获取人体原始骨髓样本以及年龄或供体的影响，人体造血功能的研究远不如小鼠那么透彻。尽管近年来在单细胞 RNA 分析方面取得了进展，但对于人类淋巴造血祖细胞和前体细胞的表型、功能和发育轨迹，我们仍知之甚少。这在很大程度上是因为过去几十年中，人们对淋巴细胞系的发育结构一直存在争议。在这里，我们描述了一种在体内对人类胎儿造血进行建模的新方法，即利用免疫缺陷的 NSG 小鼠移植新生儿 CD34 造血祖细胞（HPC），从而可以快速鉴定和分离出淋巴造血发育的中间产物。