Abstract
BackgroundIn 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.MethodsWe 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.ResultsTwelve 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.ConclusionThese 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.
Highlights
Hematopoietic stem cells (HSCs) are characterized by their capacity of both self-renewal and differentiation into blood and immune cell lineages throughout the life of the individual in a stem cell-regulating microenvironment, or HSC niche
During batch correction with canonical correlation, we observed that the two kidney samples were found well superposed in first factorial map of canonical correlation (Supplementary Figure 1A) and the shared correlation strength decreases on the 30 components of canonical correlation (Supplementary Figure 1B). t-Distributed stochastic neighbor embedding analysis on the common variable genes on the 40 principal components of the principal component analysis allowed to identify 12 clusters (Figure 1A) reproducible in both kidneys (Supplementary Figure 1C)
In unsupervised t-Distributed stochastic neighbor embedding (tSNE) analysis of the human kidney cortex, we found the left-top eccentric cluster number 9 (Figure 1A), which is principally defined by the specific expression of serglycin (SRGN) (Figures 1A, 2A and Supplementary Table 1)
Summary
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. The kidney is the site of primary hematopoiesis. The presence of HSCs in the fetal or adult kidney has not been established
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