Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis

Poulos, Michael G.; Guo, Peipei; Kofler, Natalie; Pinho, Sandra; Gutkin, Michael; Tikhonova, Anastasia; Aifantis, Iannis; Frenette, Paul S.; Kitajewski, Jan; Rafii, Shahin; Butler, Jason M.

doi:10.1016/j.celrep.2013.07.048

Cited by 225 publications

(223 citation statements)

References 52 publications

Supporting

Mentioning

216

Contrasting

Order By: Relevance

“…ECs form putative "vascular niches" that influence HSC development and maintenance, from the first definitive HSCs that emerge from the ventral wall of the dorsal aorta (6) to the ECs in the BM microenvironment that produce prohematopoietic Notch ligand jagged-1 (JAG1), which is required for homeostatic and regenerative hematopoiesis (14). Rafii et al showed that transduction of vascular endothelium with the E4ORF1 gene, which activates the Akt pathway in human ECs, augments human long-term MPP (LT-MPP) expansion through paracrine cues along key signaling pathways, including the Notch pathway (12,15,16).…”

Section: Introductionmentioning

confidence: 99%

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

et al. 2015

Self Cite

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…The VEGF2 and VE-cadherin-dependent signaling pathways play an important role in these processes [177]. Thus the fact that endothelial cells promote HSCs self-renewal was also proved in the experiments with Jagged-1 deletion using VE-cadherin-Cre when perivascular cells, including the PDGFRa + CD51 + MSCs, remained unchanged either quantitatively or functionally [178]. At the same time other authors demonstrated that CD31 hi endomucin hi -endothelial cells modulate neoangiogenesis indirectly via the Notch-signaling in the perivascular progenitors [179,180].…”

Section: Endothelial Cellsmentioning

confidence: 89%

“…Inhibition of the Notch signal in the HSCs leads to their accelerated differentiation in vitro and depletion in vivo. From this it follows that Notch-signal is crucially important in HSCs maintenance in the undifferentiated state [230], and that canonical Notch-pathway promotes HSCs self-renewal and maintenance [178].…”

Section: Notchmentioning

confidence: 99%

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Nikolskaya¹,

Butenko²

2016

JCOT

View full text Add to dashboard Cite

This article focuses on (1) the analysis of the structural-functional organization of bone marrow niches of the hematopoietic stem cells, (2) the role of the intercellular contact interactions and humoral regulation factors in these niches, in particular CXCL12, SCF and TGFβ,and (3) KEYWORDS: bone marrow, hematopoietic stem cell niche, multipotent stromal cells, hematopoiesisMaksimov and finally established at the end of the past century, it is not only the number but also entire known diversity of cell elements of immune and blood systems originate from only one type of the progenitor elements -the HSCs (unitary theory) [2].Life force and productivity of the HSCs is proved, for example, by the fact that 99.9 % of all blood-generating cells, HSCs included, in the irradiated mice can perish, and the surviving stem cells rapidly renew blood formation, including proper population as well as all types of the committed progenitors [3]. Along same sequence, the fact of non-exhaustion of blood formation after repeated damaging exposures is explained by the presence and functioning of the HSCs [1].The specialized cells of adult and fetal periods of ontogenesis, residing in the bone marrow (BM) in the quiescent state and capable, together with blood-forming microenvironment, to realize underlying programs for self-maintenance and multipotency allowing them (with maintained amount of HSCs) to release necessary amount of cells into differentiation along various directions that ultimately leads to the formation of all forms of blood elements, including immune system cells. It should be noted that the self-maintenance is not identical to the immortality. Stem cells are characterized by sufficiently long life, commensurable with entire organism's life course. Several genetic regulatory programs have been established which are of great importance in the process of HSCs self-maintenance. It is also known that stem cells in various tissues are controlled by common genetic programs maintaining their nature [4,5].It is theorized that stem cells are the clonogenic units which under certain conditions can be increased in their number at the expense Immune system is the structural-functional and interrelated commonness of the hematopoietic and stromal cells. Different in their origin, structure and functions, the populations and subpopulations of lymphoid and myeloid cells make a complete wholeness in the definite tissues and organs where they closely cooperate with non-hematopoietic elements. Constant and strictly regulated intensity of hematopoiesis with production of various cell types is also conditioned and controlled by cooperation of the hematopoietic and stromal cells. Timely repopulation of the immune system with hematopoietic cells-precursors, lymphocytes, leucocytes and stromal cells, newly maturing in the bone marrow, is the main condition for effective immune system functioning. The number of cells formed per time unit is plentiful. According to the given data, nearly 10 11 neutrophils (about 100 g of mass) per...

show abstract

“…HSCs reside in a specialized BME, which provides factors and signals necessary for HSC maintenance. Several cell types that form an integral part of the HSC BME have been identified, including cells of the osteoblast lineage, endothelial cells, and perivascular cells (13)(14)(15)(16)(17). In addition to HSC maintenance, populations of maturing hematopoietic cells have been revealed to develop within specialized BMEs, such as B lymphopoiesis (18).…”

mentioning

confidence: 99%

Retinoic Acid Receptor γ Regulates B and T Lymphopoiesis via Nestin-Expressing Cells in the Bone Marrow and Thymic Microenvironments

Joseph

Nota

Fletcher

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Vitamin A has essential but largely unexplained roles in regulating lymphopoiesis. We have previously shown that retinoic acid receptor (RAR) γ–deficient mice have hematopoietic defects, some phenotypes of which were microenvironment induced. Bone marrow (BM) microenvironment cells identified by either their expression of nestin (Nes) or osterix (Osx) have previously been shown to have roles in regulating lymphopoiesis. We therefore conditionally deleted Rarγ in Nes- or Osx-expressing microenvironment cells. Osx cell–specific deletion of Rarγ had no impact on hematopoiesis. In contrast, deletion of Rarγ in Nes-expressing cells resulted in reductions in peripheral blood B cells and CD4+ T cells, accompanied by reductions of immature PreB cells in BM. The mice lacking Rarγ in Nes-expressing cells also had smaller thymi, with reductions in double-negative 4 T cell precursors, accompanied by reduced numbers of both TCRβlow immature single-positive CD8+ cells and double-positive T cells. In the thymus, Nes expression was restricted to thymic stromal cells that expressed cerebellar degeneration-related Ag 1 and lacked expression of epithelial cell adhesion molecule. These cells expressed platelet-derived growth factor α and high transcript levels of Rars, Cxcl12, and stem cell factor (Scf). Short-term treatment of mice with all-trans retinoic acid resulted in increased PreB lymphopoiesis in BM and an increase in thymic double-negative 4 T cells, inverse to that observed upon Nes cell-specific deletion of Rarγ. Collectively, these studies show that RARγ is a regulator of B and T lymphopoiesis via Nes-expressing cells in the BM and thymic microenvironments, respectively.

show abstract

Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis

Cited by 225 publications

References 52 publications

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Retinoic Acid Receptor γ Regulates B and T Lymphopoiesis via Nestin-Expressing Cells in the Bone Marrow and Thymic Microenvironments

Contact Info

Product

Resources

About