期刊
NATURE CELL BIOLOGY
卷 22, 期 1, 页码 60-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41556-019-0445-8
关键词
-
类别
资金
- National Health and Medical Research Council of Australia [GNT1117596, GNT1079004, GNT1068866, GNT1129861, GNT1138717, GNT1123277]
- Australian Research Council Special Research Initiative in Stem Cells (Stem Cells Australia)
- Children's Cancer Research Foundation (Australia)
- Stafford Fox Medical Research Foundation
- Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme
- Victorian Government's Operational Infrastructure Support Program
Defining the ontogeny of the human adaptive immune system during embryogenesis has implications for understanding childhood diseases including leukaemias and autoimmune conditions. Using RAG1:GFP human pluripotent stem cell reporter lines, we examined human T-cell genesis from pluripotent-stem-cell-derived haematopoietic organoids. Under conditions favouring T-cell development, RAG1+ cells progressively upregulated a cohort of recognized T-cell-associated genes, arresting development at the CD4+CD8+ stage. Sort and re-culture experiments showed that early RAG1+ cells also possessed B-cell, myeloid and erythroid potential. Flow cytometry and single-cell-RNA-sequencing data showed that early RAG1+ cells co-expressed the endothelial/haematopoietic progenitor markers CD34, VECAD and CD90, whereas imaging studies identified RAG1+ cells within CD31+ endothelial structures that co-expressed SOX17+ or the endothelial marker CAV1. Collectively, these observations provide evidence for a wave of human T-cell development that originates directly from haemogenic endothelium via a RAG1+ intermediate with multilineage potential. Motazedian et al. examine human T-cell genesis in haematopoietic organoids and show that RAG1 marks multipotent T-cell progenitors that arise directly from the haemogenic endothelium.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据