Cell cycle regulation of hematopoietic stem or progenitor cells

Hao, Sha; Chen, Chen; Cheng, Tao

doi:10.1007/s12185-016-1984-4

Cited by 55 publications

(41 citation statements)

References 99 publications

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“…We have also performed a gene expression analysis of other 15 genes supposed to be involved in HSC self-renewal, including Runx1, FoxO3a, SMAD4, Angpt1, Tie2, p16, Notch1, Bmi-1, HoxB4, OCT4 and Nanog [5, 6, 34–38]. None of these 12 genes showed differences in expression between the NN and the LN.…”

Section: Resultsmentioning

confidence: 99%

“…These properties are necessary for the maintenance of the HSC pool and important in the development and regeneration of the hematopoietic system under normal and stressful conditions [1–3]. HSC reside in specialized niches [4] in the bone marrow (BM) with which they interact continuously, influencing these properties [5, 6]. Multiple cellular types, soluble factors and extracellular matrix components form this niche [7, 8].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the relationship between cell cycle regulators (cytokines, cyclin and cyclin-regulators, transcription factors, microRNA, etc.) and HSC self-renewal has been partially elucidated [5, 15]. …”

Section: Introductionmentioning

confidence: 99%

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Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche

Vanegas

Vernot

2017

Exp Hematol Oncol

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BackgroundLeukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells.MethodsA leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line. After 3 days, the REH-conditioned medium was removed and freshly isolated CD34+ at a density of up to 100,000 cells/ml were added to the leukemic niche. CD34+ cell evaluations (cell cycle, self-renewal gene expression and migration capacity) were performed after 3 further days of co-culture. Additionally, we preliminary investigated the soluble factors present in the leukemic niche and their effect on the mesenchymal stem cells. Statistical significance was assessed by Student’s t test or the nonparametric test Kolmogorov–Smirnov.ResultsBy co-culturing normal mesenchymal stem cells with the REH-conditioned medium we showed that hematopoietic stem cells, normally in a quiescent state, enter cell cycle and proliferate. This loss of quiescence was accompanied by an increased expression of Ki-67 and c-Myc, two well-known cell proliferation-associated markers. Two central regulators of quiescence GATA2 and p53 were also down regulated. Importantly, two genes involved in HSC self-renewal, Klf4 and the histone–lysine N-methyltransferase enzyme Ezh2, were severely affected. On the contrary, c-Kit expression, the stem cell factor receptor, was upregulated in hematopoietic stem cells when compared to the normal niche. Interestingly, mesenchymal stem cells incubated with the REH-conditioned medium stopped growing, showed a flattened morphology with the appearance of small vacuoles, and importantly, became positive for the senescence-associated beta-galactosidase activity. Evaluation of the leukemic-conditioned medium showed increased IL-6 and IL-8, suggesting that these cytokines could be responsible for the observed changes.ConclusionsOur results showed that quiescence and self-renewal are severely affected in this leukemic niche. This in vitro leukemic niche, established without leukemic cells, will facilitate HSC gene expression evaluation and the development of therapeutic agents aimed to neutralize soluble factors and the cell signaling pathways involved in HSC alterations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-016-0062-1) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche

Vanegas

Vernot

2017

Exp Hematol Oncol

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“…The self-renewal capacity is necessary for homeostasis because mature blood cells have a short lifetime. 4 HSPCs can be retrieved from BM, umbilical cord blood (UCB), and peripheral blood (PB) by apheresis after mobilizing HSPCs from BM to PB under the effect of granulocyte-colony stimulating factor (G-CSF). HPCs are uni-, bi-, or multi-potent, which have differentiation potential into various types of blood cells with limited self-renewal capacity.…”

Section: Hematopoiesis and Hematopoietic Stem And Progenitor Cells (Hmentioning

confidence: 99%

“…3 Self-renewal is essential for maintaining the HSPC reconstitution and is therefore a prerequisite for lifelong hematopoiesis. 4 Most HSPCs are quiescent and in G0 phase of cell cycle, 5,6 and daily hematopoiesis is largely maintained by highly proliferative downstream HSPCs. 7 Cellular actions of HSPCs are controlled by both intrinsic cellular factors such as transcriptional regulatory networks, as well as extrinsic cellular factors like growth factors, cytokines, chemokines and microvesicles (MVs); for example, G-CSF, CXCL12, and transforming growth factor-β (TGF-β).…”

Section: Introductionmentioning

confidence: 99%

Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic Stem Cells

Aqmasheh¹,

Shamsasanjan²,

Akbarzadehlaleh³

et al. 2017

Adv Pharm Bull

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Hematopoiesis is a balance among quiescence, self-renewal, proliferation, and differentiation, which is believed to be firmly adjusted through interactions between hematopoietic stem and progenitor cells (HSPCs) with the microenvironment. This microenvironment is derived from a common progenitor of mesenchymal origin and its signals should be capable of regulating the cellular memory of transcriptional situation and lead to an exchange of stem cell genes expression. Mesenchymal stem cells (MSCs) have self-renewal and differentiation capacity into tissues of mesodermal origin, and these cells can support hematopoiesis through release various molecules that play a crucial role in migration, homing, self-renewal, proliferation, and differentiation of HSPCs. Studies on the effects of MSCs on HSPC differentiation can develop modern solutions in the treatment of patients with hematologic disorders for more effective Bone Marrow (BM) transplantation in the near future. However, considerable challenges remain on realization of how paracrine mechanisms of MSCs act on the target tissues, and how to design a therapeutic regimen with various paracrine factors in order to achieve optimal results for tissue conservation and regeneration. The aim of this review is to characterize and consider the related aspects of the ability of MSCs secretome in protection of hematopoiesis.

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Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

et al. 2019

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Transcription factor (TF)‐based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial‐like precursors that generate hematopoietic stem progenitor (HSPC)‐like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC‐like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell frequency. Altogether, we demonstrate an improved human hemogenic induction protocol that could provide a valuable human in vitro model of hematopoiesis for disease modeling and a platform for cell‐based therapeutics. Database Gene expression data are available in the Gene Expression Omnibus (GEO) database under the accession number http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130361.

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Cell cycle regulation of hematopoietic stem or progenitor cells

Abstract: researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

Cited by 55 publications

References 99 publications

Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche

Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche

Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic Stem Cells

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

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