Abstract
SummaryHuman hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. Although we previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. Here, we show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. From a clinical perspective, the efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. We quantitatively show that this capacity dramatically declines in the umbilical cord blood compared with HSCs in the AGM region. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells.
Highlights
Previous analyses using transplantations into adult NOD.Cg-Prkdcscid Il2rgtm1Wjl/Sz (NSG) mice showed that the first human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17 and possess a substantial self-renewal potential (Ivanovs et al, 2011, 2014)
A single-cell suspension prepared from an individual AGM region was split into five equal parts and transplanted into five primary NSG recipient mice
To assess daughter HSC numbers generated by a single AGM region HSC, 5–9 months after the primary transplantation the bone marrow (BM) of each engrafted primary recipient was retransplanted in limiting dilutions into a cohort of 20 secondary recipients split into four groups
Summary
Human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. We previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. We show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. The efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells
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