Mechanisms of self-renewal in hematopoietic stem cells

Wang, Zhao; Ema, Hideo

doi:10.1007/s12185-015-1919-5

Cited by 27 publications

(22 citation statements)

References 121 publications

(119 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

“…Under homeostatic conditions, most HSC exist in the G0 phase of the cell cycle with signals from the niche used to preserve a quiescent state as a protective mechanism against cell damage and exhaustion [6]. Other signals stimulate the appearance of cell progenitors and thus cell cycle entry and proliferation [11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Vanegas

Vernot

2017

Exp Hematol Oncol

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Vanegas

Vernot

2017

Exp Hematol Oncol

View full text Add to dashboard Cite

show abstract

“…As CTHs constituem menos de um por cento das células da MO e são caracterizadas pela capacidade de assumir diferentes destinos, incluindo autorrenovação, quiescência e diferenciação [6][7][8]. Essas funções permitem que essa pequena porção de células tenha papel fundamental no desenvolvimento, manutenção e regeneração do sistema hematopoético [9,10].…”

Section: Hematopoeseunclassified

“…(B) Quantificação da bioluminescência emitida pelas células HEL luc nos dias D+7, D+14 e D+21. A intensidade de bioluminescência é medida em fótons por segundo e está expressa em Log10 . O sinal da bioluminescência é diretamente proporcional ao número de células HEL que expressam luciferase biologicamente ativa.…”

unclassified

Inibição farmacológica dos substratos do receptor de insulina em neoplasia mieloproliferativa JAK2<sup>V617F</sup>

Fenerich¹

View full text Add to dashboard Cite

Quero agradecer primeiramente a Deus por me fortalecer diariamente, guiando meus passos e abençoando minha trajetória. À minha orientadora, Prof. Dra. Fabíola Traina, pela oportunidade e por todo o crescimento profissional e pessoal proporcionado. Esta parceria que se iniciou na iniciação científica e se estendeu pelo mestrado representou um período de intenso aprendizado, que levarei por toda a minha jornada profissional.

show abstract

Comparative hematopoiesis and signal transduction in model organisms

Gautam

Chimata

Gutti

et al. 2021

Journal Cellular Physiology

View full text Add to dashboard Cite

Hematopoiesis is a continuous phenomenon involving the formation of hematopoietic stem cells (HSCs) giving rise to diverse functional blood cells. This developmental process of hematopoiesis is evolutionarily conserved, yet comparably different in various model organisms. Vertebrate HSCs give rise to all types of mature cells of both the myeloid and the lymphoid lineages sequentially colonizing in different anatomical tissues. Signal transduction in HSCs facilitates their potency and specifies branching of lineages. Understanding the hematopoietic signaling pathways is crucial to gain insights into their deregulation in several blood‐related disorders. The focus of the review is on hematopoiesis corresponding to different model organisms and pivotal role of indispensable hematopoietic pathways. We summarize and discuss the fundamentals of blood formation in both invertebrate and vertebrates, examining the requirement of key signaling nexus in hematopoiesis. Knowledge obtained from such comparative studies associated with developmental dynamics of hematopoiesis is beneficial to explore the therapeutic options for hematopoietic diseases.

show abstract

Mechanisms of self-renewal in hematopoietic stem cells

Cited by 27 publications

References 121 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

Inibição farmacológica dos substratos do receptor de insulina em neoplasia mieloproliferativa JAK2<sup>V617F</sup>

Comparative hematopoiesis and signal transduction in model organisms

Contact Info

Product

Resources

About