Harnessing the Complexity of Normal and Pathological Hematopoietic Supportive Niches

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Background

Hematopoietic stem cells (HSCs) develop in discrete anatomical niches during embryogenesis, migrating from the aorta-gonad-mesonephros (AGM) region to the fetal liver, and finally after birth, to the bone marrow (BM). For their maintenance all life long, HSC and their progeny have to be safeguarded in the BM from environmental insults or uncontrolled immune reactions. Mesenchymal, endothelial, and hematopoietic cells themselves form nurturing and protective BM niches that regulate maintenance, quiescence, and differentiation of both immature and mature immune cells. It is now clear that a functional crosstalk is established between partner cells through direct interactions and reciprocal secretion of growth factors. However, a breach in this equilibrium can lead to the development of hematological neoplasias, which remodel the BM ecosystem to their own advantage, thus contributing to therapy-resistance and disease relapse.

Most knowledge on the role of normal and pathological BM niches has emerged from the identification of niches controlling HSC self-renewal and B lymphopoiesis. Nevertheless, and despite tremendous progress in high throughput analysis at the single-cell level, the supportive signals transmitted by the BM microenvironment and at the origin of resistance to therapies in pathological conditions are still poorly understood. It is therefore of crucial interest to decipher the mechanisms involved in niche development and function in order to identify new therapeutic targets.

With this Research Topic, we aim to gather Original Research and Review articles related to the supportive role of the bone marrow microenvironment on normal and pathological hematopoiesis as well as on recirculating mature immune cells. We also encourage the submission of manuscripts prospecting the concept of hematopoietic progenitor supportive niches during fetal life and upon stress in extra-medullary locations. Finally, we will consider with great interest studies focusing on hematopoietic niches in model organisms.

We will thus welcome articles that cover, but are not limited to, the following topics:

1. Cellular niches supporting HSC self-renewal and development
2. Influence of bone marrow mesenchymal/endothelial niches on lymphoid/myeloid cell development
3. Vascular organization of the BM and influence on the hematopoietic system
4. Regulation of the BM ecosystem by the nervous system
5. Global topography of BM niches
6. BM niches for mature immune cells
7. Functional and structural remodeling of BM mesenchymal/endothelial niches in leukemia
8. New therapeutic strategies targeting the BM pathological niches
9. Therapeutic use of mesenchymal cells in the treatment of hematopoietic diseases
10. BM niches and aging
11. Immune regulation in normal and pathological hematopoietic niches
12. Novel technological approaches to dissect BM niche heterogeneity
13. Use of alternative models to study early hematopoietic niches

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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