Hwang Jin Wook, Desterke Christophe, Loisel-Duwattez Julien, Griscelli Frank, Bennaceur-Griscelli Annelise, Turhan Ali G
INSERM U935/UA09, Université Paris-Saclay, Villejuif, France.
ESTeam Paris Sud, Université Paris Sud, Villejuif, France.
Front Cell Dev Biol. 2021 Jun 11;9:668833. doi: 10.3389/fcell.2021.668833. eCollection 2021.
In mammalians, hematopoietic stem cells (HSCs) arise in the dorsal aorta from the hemogenic endothelium, followed by their migration to the fetal liver and to the bone marrow. In zebrafish, the kidney is the site of primary hematopoiesis. In humans, the presence of HSCs in the fetal or adult kidney has not been established.
We analyzed the presence of HSC markers in the human fetal kidneys by analysis of single-cell datasets. We then analyzed in kidney organoids derived from induced pluripotent stem cells (iPSCs) the presence of hematopoietic markers using transcriptome analyses.
Twelve clusters were identified as stromal, endothelial, and nephron cell type-specific markers in the two fetal stage (17 weeks) kidney datasets. Among these, the expression of hematopoietic cells in cluster 9 showed an expression of primitive markers. Moreover, whole transcriptome analysis of our iPSC-derived kidney organoids revealed induction of the primitive hematopoietic transcription factor RUNX1 as found in the human fetal kidney cortex.
These finding support the presence of cells expressing HSC transcriptome in the human kidney. The mechanisms of the appearance of the cells with the same transcriptional features during iPSC-derived kidney organoid generation require further investigation.
在哺乳动物中，造血干细胞（HSCs）起源于背主动脉的生血内皮，随后迁移至胎儿肝脏和骨髓。在斑马鱼中，肾脏是主要造血部位。在人类中，胎儿或成人肾脏中造血干细胞的存在尚未得到证实。
我们通过分析单细胞数据集来分析人类胎儿肾脏中造血干细胞标志物的存在情况。然后，我们使用转录组分析方法，对源自诱导多能干细胞（iPSCs）的肾脏类器官中的造血标志物进行分析。
在两个胎儿阶段（17周）的肾脏数据集中，鉴定出了12个簇作为基质、内皮和肾单位细胞类型特异性标志物。其中，第9簇中造血细胞的表达显示出原始标志物的表达。此外，我们对源自iPSC的肾脏类器官进行的全转录组分析显示，在人类胎儿肾皮质中发现的原始造血转录因子RUNX1被诱导表达。
这些发现支持人类肾脏中存在表达造血干细胞转录组的细胞。在源自iPSC的肾脏类器官生成过程中，具有相同转录特征的细胞出现的机制需要进一步研究。
