Hematopoietic progenitors polarize in contact with bone marrow stromal cells in response to SDF1

Abstract

The fate of hematopoietic stem and progenitor cells (HSPCs) is regulated by their interaction with stromal cells in the bone marrow. However, the cellular mechanisms regulating HSPC interaction with these cells and their potential impact on HSPC polarity are still poorly understood. Here we evaluated the impact of cell–cell contacts with osteoblasts or endothelial cells on the polarity of HSPC. We found that an HSPC can form a discrete contact site that leads to the extensive polarization of its cytoskeleton architecture. Notably, the centrosome was located in proximity to the contact site. The capacity of HSPCs to polarize in contact with stromal cells of the bone marrow appeared to be specific, as it was not observed in primary lymphoid or myeloid cells or in HSPCs in contact with skin fibroblasts. The receptors ICAM, VCAM, and SDF1 were identified in the polarizing contact. Only SDF1 was independently capable of inducing the polarization of the centrosome–microtubule network.

Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours

“…tumours. They may also be related to protrusive structures named magnupodia recently described in polarised migrating haematopoietic stem cells [136]. Chemotactic and EMT promoting signals such as SDF1-α induce podia formation in leukaemia [140] and haematopoietic stem cells [136].…”

“…Podia are tubular membrane projections formed by protrusive activity and sustained by integrins and CD44 mediated adhesions that are observed in haematopoietic stem cells [136,137] as well as in leukaemia [137] and multiple myeloma cells [138] (Figure 3). These structures may be reminiscent of the McTNs assembled by cells undergoing EMT in solid The modulation of the signalosome in podosomes may not only affect the migratory capacity of haematological tumour cells but also the expression of genes involved in cell survival, proliferation and secretion of cytokines, critical mechanisms involved in cancer progression, immunosuppression and drug resistance.…”

“…They may also be related to protrusive structures named magnupodia recently described in polarised migrating haematopoietic stem cells [136]. Chemotactic and EMT promoting signals such as SDF1-α induce podia formation in leukaemia [140] and haematopoietic stem cells [136]. Podia assembly requires the activation of the degradative enzyme elastase in leukaemia cells [140] but the possible extracellular matrix degradation function of podia has not been demonstrated.…”

“…Interestingly, inhibition of elastase activity in leukaemia cells inhibited cell migration and promoted proliferation [140], a phenotype similar to that of cells undergoing MET. However, no clear link between podia formation and Chemotactic and EMT promoting signals such as SDF1-α induce podia formation in leukaemia [140] and haematopoietic stem cells [136]. Podia assembly requires the activation of the degradative enzyme elastase in leukaemia cells [140] but the possible extracellular matrix degradation function of podia has not been demonstrated.…”

“…Podia are tubular membrane projections formed by protrusive activity and sustained by integrins and CD44 mediated adhesions that are observed in haematopoietic stem cells [ 136 , 137 ] as well as in leukaemia [ 137 ] and multiple myeloma cells [ 138 ] ( Figure 3 ). These structures may be reminiscent of the McTNs assembled by cells undergoing EMT in solid tumours.…”