Abstract
The fetal liver (FL) is a source of hematopoietic stem and progenitor cells (HSPCs) for transplantation. However, whether FL-HSPCs collected at distinct developmental stages reconstitute similarly or differently in the recipient bone marrow (BM) remains undetermined. We examined this problem in a congeneic mouse transplantation model. We first analyzed the lineage components of FL from 12.5 days post-fertilization (dpf) to 18.5 dpf. The myeloid and lymphoid cells were dynamic in absolute number and ratio. The largest difference was between 12.5 and 16.5 dpf. The FL-HSPCs (Lin−CD150+CD48−) at these two time points were then respectively transplanted into the recipients. The difference in lineage reconstitution was undetectable at week 4 or 6 post-transplantation and afterward, indicating that the BM environment assimilated the transplanted cells. Profiling lineage-regulation genes of input and output HSPCs showed that the expression levels were much different in the former and almost the same in the engrafted HSPCs. Therefore, the recipient BM microenvironment could determine the developmental lineage-trends of FL-HSPCs.
Highlights
Lack of proper bone marrow (BM) donors remains a major issue in hematopoietic stem cell transplantation therapy, in unexpected disasters, such as nuclear crisis
Given that fetal liver (FL) is used as a source of hematopoietic stem and progenitor cells (HSPCs) for transplantation, a key issue would be whether FL-HSPCs collected at distinct developmental stages reconstitute or differently in the recipient BM
The results showed that the HSPCs from 16.5 dpf FL had increased myeloid differentiation potential compered with the HSPCs of 12.5 dpf FL (Figure 2C)
Summary
Lack of proper bone marrow (BM) donors remains a major issue in hematopoietic stem cell transplantation therapy, in unexpected disasters, such as nuclear crisis. Alternative sources of hematopoietic stem and progenitor cells (HSPCs) have been proposed, which include the fetal liver (FL) [1, 2]. FL is the primary fetal hematopoietic organ in which HSPCs undergo expansion and differentiation before migrating to the BM at the perinatal stage [3]. Given that FL is used as a source of HSPCs for transplantation, a key issue would be whether FL-HSPCs collected at distinct developmental stages reconstitute or differently in the recipient BM. To address this issue, a congeneic mouse transplantation model was used in this study
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