Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development

Bowers, Marisa; Zhang, Bin; Ho, YinWei; Agarwal, Puneet; Chen, Ching-Cheng; Bhatia, Smita

doi:10.1182/blood-2014-06-582924

Cited by 119 publications

(83 citation statements)

References 25 publications

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“…These studies argue that osteoblasts may be dispensable for HSC maintenance and self-renewal. Interestingly, Bhatia et al recently reported that osteoblast ablation did not result in a decrease in LTHSCs, but their long-term reconstitution and self-renewal capacities were impaired [33]. Tie-2-expressing HSCs could adhere to osteoblasts and stay in the quiescent state induced by angiopoietin-1 [34].…”

Section: Niche Cells Regulating Hscsmentioning

confidence: 99%

Mechanisms of self-renewal in hematopoietic stem cells

Wang

Ema

2015

Int J Hematol

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Section: Niche Cells Regulating Hscsmentioning

confidence: 99%

Mechanisms of self-renewal in hematopoietic stem cells

Wang

Ema

2015

Int J Hematol

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“…Some researchers tended to exclude the osteoblast niche from the HSC functional supporting cells because deleting either Scf or Cxcl12 using Col2.3-Cre did not affect HSC function in mice. However, recent evidence has shown that Col2.3-Cre induced osteoblast oblation in mice impaired HSC self-renewal function, though the overall number of HSCs did not significantly change [42,43]. This suggests that Col2.3-Cre marked osteoblasts might produce other unknown factors that contribute to maintaining HSC self-renewal potential.…”

Section: Identification Of Hsc Regulating Cells-a "Taking One Out" Stmentioning

confidence: 66%

Regulation of hematopoietic stem cells in the niche

Zhao

2015

Sci. China Life Sci.

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Hematopoiesis provides a suitable model for understanding adult stem cells and their niche. Hematopoietic stem cells (HSCs) continuously produce blood cells through orchestrated proliferation, self-renewal, and differentiation in the bone marrow (BM). Within the BM exists a highly organized microenvironment termed "niche" where stem cells reside and are maintained. HSC niche is the first evidence that a microenvironment contributes to protecting stem cell integrity and functionality in mammals. Although multiple models exist, recent progress has principally elucidated the cellular complexity of the HSC niche that maintains and regulates HSCs in BM. Here we introduce the development and summarize the achievements of HSC niche studies. hematopoietic stem cells, niche, regeneration Citation:Zhao M, Li LH. Regulation of hematopoietic stem cells in the niche.

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“…Apparently, there took place a compensatory activation of the extramedullary hematopoiesis in the spleen and in the liver [80]. As a result of ablation of endosteal osteoblasts, the process of LT-HSCs self-renewal was disturbed while leukemia development was accelerated [81]. Thus essential role of the osteoblast that intercellular contacts in vitro produce a considerable influence on the functional, phenotypic and clonogenic properties of HSCs.…”

Section: Cd38mentioning

confidence: 97%

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

Nikolskaya¹,

Butenko²

2016

JCOT

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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...

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Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development

Abstract: • Bone marrow OB ablation leads to reduced quiescence, long-term engraftment, and self-renewal capacity of hematopoietic stem cells.• Significantly accelerated leukemia development and reduced survival are seen in transgenic BCR-ABL mice following OB ablation.

Cited by 119 publications

References 25 publications

Mechanisms of self-renewal in hematopoietic stem cells

Mechanisms of self-renewal in hematopoietic stem cells

Regulation of hematopoietic stem cells in the niche

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

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