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Even, Y.

Publications and source records attributed to Even, Y..

2 recordsLinked to original sources
bioRxiv2021

After migration into blood circulation, hematopoietic stem cells can stably self-renew and maintain bone marrow while being skewed toward myeloid lineage when submitted to serial transplantation.

Hematopoietic stem cells (HSCs) mainly reside in bone marrow (BM) within niches providing an appropriate environment for their survival and self-renewal. Although, small numbers of HSCs can quit their residing environment to migrate into blood circulation and re-engraft elsewhere in BM. Mobilizing agents such as granulocyte colony stimulating factor (G-CSF) can amplify this process by inducing massive HSC mobilization into blood circulation. This method is widely used in clinics to treat hematological disorders. However, in physiological conditions, the properties of HSCs after migration (called migratory HSCs) remain incompletely characterized. In this study, we investigated the capacity of migratory HSCs to self-renew, reconstitute and maintain BM. We show that after migration, HSCs can stably self-renew and maintain BM in homeostasis. However, while stably repopulating BM of irradiated recipients, migratory HSCs show a defect in lymphoid lineage reconstitution when subjected to serial transplantations. Our findings provide interesting knowledge on HSC properties after migration, which may benefits therapeutic research on HSC-based therapies to treat hematological disorders.

cell biology↗
bioRxiv2021

The parathyroid hormone-dependent activation of osteoblasts enhances hematopoietic stem cell migration and reduces their engraftment abilities

Hematopoietic stem cells (HSCs) in the bone marrow (BM) reside in HSC niches ensuring their maintenance. The HSC niche is made up of perivascular and trabecular cells including osteoblasts whose role on HSCs remains to be clearly defined. Increased numbers of osteoblasts have been observed in the CL2 transgenic mouse expressing a constitutively activated form of the parathyroid hormone (PTH)/PTH-related peptide receptor. This mouse model mimicking PTH anabolic effect has also been described to exhibit increased numbers of the BM stem/progenitor population. Furthermore, PTH is known to induce BM stem/progenitor cell migration into blood circulation. However PTH role on long-term repopulating HSCs (LT-HSCs) is incompletely known. Here we show that CL2 BM contains a regular proportion of LT-HSCs, suggesting that osteoblasts may not be a determinant of LT-HSC numbers but act mainly on more mature progenitors. We further show increased LT-HSC migration in CL2 mice correlated with higher granulocyte colony-stimulating factor (G-CSF) serum levels, supporting the idea that PTH can enhance the migration of LT-HSCs. Finally, we found a defect in the ability of CL2 BM HSCs to reconstitute irradiated BM suggesting that PTH activation of osteoblasts negatively influences abilities of HSC population to engraft and reconstitute irradiated BM. In summary, our study highlights new insights into the role of the PTH-dependent activation of osteoblasts on LT-HSC migration and their BM repopulation abilities. Our findings will be useful to improve treatments on hematological disorders, especially therapies involving HSC harvest and transplantation.

cell biology↗