Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche

CXC motif chemokine receptor type 4 (CXCR4) is associated with normal and abnormal development, including oncogenesis. The ligand of CXCR4 is stromal cell-derived factor (SDF), also known as CXC motif ligand (CXCL) 12. Through the SDF-1/CXCR4 axis, both homing and migration of hematopoietic (stem) cells are regulated through niches in the bone marrow. Outside of the bone marrow, however, SDF-1 can recruit CXCR4-positive cells from the bone marrow. SDF/CXCR4 has been implicated in the maintenance and/or differentiation of stemness, and tissue-derived stem cells can be associated with SDF-1 and CXCR4 activity. CXCR4 plays a role in multiple pathways involved in carcinogenesis and other pathologies. Here, we summarize reports detailing the functions of CXCR4. We address the molecular signature of CXCR4 and how this molecule and cells expressing it are involved in either normal (maintaining stemness or inducing differentiation) or abnormal (developing cancer and other pathologies) events. As a constituent of stem cells, the SDF-1/CXCR4 axis influences downstream signal transduction and the cell microenvironment.

https://www.mdpi.com/2073-4409/8/2/185/pdf

Involvement of CXCR4 in Normal and Abnormal Development.

Neural stem cell niche heterogeneity.

The premetastatic niche formed by primary tumor–derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779–86. ©2018 AACR .

/pdf/pericytes-in-the-premetastatic-niche-45y8vaa0if.pdf

Pericytes in the Premetastatic Niche

Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.1375

Glioblastoma-activated pericytes support tumor growth via immunosuppression

Platelets are released from megakaryocytes. The bone marrow has been proposed to be the major site where this process occurs. Lefrancais et al. (2017) using state-of-the-art techniques including two-photon microscopy, in vivo lineage-tracing technologies, and sophisticated lung transplants reveal that the lung is also a primary site for platelet biogenesis. Strikingly, lung megakaryocytes can completely reconstitute platelet counts in the blood in mice with thrombocytopenia. This study also shows that hematopoietic progenitors, with capacity to repopulate the bone marrow after irradiation, are present in the lungs. This work brings a novel unexpected role for the lung as a niche for hematopoiesis. The emerging knowledge from this research may be important for the treatment of several disorders.

/pdf/lung-as-a-niche-for-hematopoietic-progenitors-3viosglm5s.pdf

Luanny Souto de Barros Silva

Papers

Lung as a Niche for Hematopoietic Progenitors