scholarly journals Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells

Cell Reports ◽  
2017 ◽  
Vol 20 (13) ◽  
pp. 3199-3211 ◽  
Author(s):  
Sarah Rodrigues-Moreira ◽  
Stéphanie G. Moreno ◽  
Giulia Ghinatti ◽  
Daniel Lewandowski ◽  
Françoise Hoffschir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Low Dose ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Dose Irradiation

3164 – HOXB5 CONFERS INCREASED STRESS TOLERANCE AND MAINTENANCE OF SELF-RENEWAL TO THE HEMATOPOIETIC STEM CELLS

2019 ◽  
Vol 76 ◽  
pp. e2
Author(s):  
Masanori Miyanishi ◽  
Kevin Kao ◽  
Taro Sakamaki ◽  
James Chen ◽  
Katsuyuki Nishi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Stress Tolerance ◽  
Self Renewal ◽  
Hematopoietic Stem

scholarly journals Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

Cell Reports ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 964-975 ◽  
Author(s):  
Heather A. Himburg ◽  
Jeffrey R. Harris ◽  
Takahiro Ito ◽  
Pamela Daher ◽  
J. Lauren Russell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Vascular Niche ◽  
Bone Marrow Vascular Niche

3065 – ETV6-RUNX1 ENHANCES THE SELF-RENEWAL OF HEMATOPOIETIC STEM CELLS AND CORRUPTS EARLY LYMPHOID DIFFERENTIATION

2020 ◽  
Vol 88 ◽  
pp. S58
Author(s):  
Mohamed Eldeeb ◽  
Jonas Ungerbäck ◽  
Mikael Sigvardsson ◽  
David Bryder
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
The Self ◽  
Self Renewal ◽  
Hematopoietic Stem

Control of self-renewal activity of hematopoietic stem cells by spred1

2014 ◽  
Vol 42 (8) ◽  
pp. S61
Author(s):  
Yuko Tadokoro ◽  
Koji Eto ◽  
Hideo Ema ◽  
Satoshi Yamazaki ◽  
Akihiko Yoshimura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Self Renewal ◽  
Hematopoietic Stem

Single-cell analyses show TGF-b1 reduces self-renewal and myeloid differentiation potentials in hematopoietic stem cells

2017 ◽  
Vol 53 ◽  
pp. S109-S110
Author(s):  
Xiaofang Wang ◽  
Fang Dong ◽  
Sen Zhang ◽  
Wanzhu Yang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Myeloid Differentiation ◽  
Self Renewal ◽  
Hematopoietic Stem

scholarly journals Maintenance of Hematopoietic Stem Cells Through Regulation of Wnt and mTOR Pathways.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2309-2309
Author(s):  
Jian Huang ◽  
Peter S. Klein
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Signaling Pathways ◽  
Glycogen Synthase ◽  
Dependent Manner ◽  
Mtor Inhibition ◽  
Self Renewal ◽  
Hematopoietic Stem

Abstract Abstract 2309 Hematopoietic stem cells (HSCs) maintain the ability to self-renew and to differentiate into all lineages of the blood. The signaling pathways regulating hematopoietic stem cell (HSCs) self-renewal and differentiation are not well understood. We are very interested in understanding the roles of glycogen synthase kinase-3 (Gsk3) and the signaling pathways regulated by Gsk3 in HSCs. In our previous study (Journal of Clinical Investigation, December 2009) using loss of function approaches (inhibitors, RNAi, and knockout) in mice, we found that Gsk3 plays a pivotal role in controlling the decision between self-renewal and differentiation of HSCs. Disruption of Gsk3 in bone marrow transiently expands HSCs in a b-catenin dependent manner, consistent with a role for Wnt signaling. However, in long-term repopulation assays, disruption of Gsk3 progressively depletes HSCs through activation of mTOR. This long-term HSC depletion is prevented by mTOR inhibition and exacerbated by b-catenin knockout. Thus GSK3 regulates both Wnt and mTOR signaling in HSCs, with opposing effects on HSC self-renewal such that inhibition of Gsk3 in the presence of rapamycin expands the HSC pool in vivo. In the current study, we found that suppression of the mammalian target of rapamycin (mTOR) pathway, an established nutrient sensor, combined with activation of canonical Wnt/ß-catenin signaling, allows the ex vivo maintenance of human and mouse long-term HSCs under cytokine-free conditions. We also show that combining two clinically approved medications that activate Wnt/ß-catenin signaling and inhibit mTOR increases the number of long-term HSCs in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Deletion of PI3-Kinase Promotes Myelodysplasia Through Dysregulation of Autophagy in Hematopoietic Stem Cells

2020 ◽  
Author(s):  
Kristina Ames ◽  
Imit Kaur ◽  
Yang Shi ◽  
Meng Tong ◽  
Taneisha Sinclair ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Akt Pathway ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Phosphoinositide 3 Kinase

AbstractHematopoietic stem cells (HSCs) maintain the blood system through a delicate equilibrium between self-renewal and differentiation. Most hematopoietic growth factors and cytokines signal through phosphoinositide 3-kinase (PI3K) via three Class IA catalytic PI3K isoforms (P110α, β, and δ), encoded by Pik3ca, Pik3cb, and Pik3cd, respectively. The PI3K/AKT pathway is commonly activated in acute myeloid leukemia (AML), and PI3K is a common therapeutic target in cancer. However, it is not known whether PI3K is required for HSC differentiation or self-renewal. We previously demonstrated that individual PI3K isoforms are dispensable in HSCs1,2. To determine the redundant roles of PI3K isoforms in HSCs, we generated a triple knockout (TKO) mouse model with deletion of all three Class IA PI3K isoforms in the hematopoietic system. Surprisingly, we observed significant expansion of TKO HSCs after transplantation, with decreased differentiation capacity and impaired multilineage repopulation. Additionally, the bone marrow of TKO mice exhibited myelodysplastic features with chromosomal abnormalities. Interestingly, we found that macroautophagy (thereafter autophagy) is impaired in TKO HSCs, and that pharmacologic induction of autophagy improves their differentiation. Therefore, we have uncovered important roles for PI3K in autophagy regulation in HSCs to maintain the balance between self-renewal and differentiation.

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