scholarly journals USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells

Cell Reports ◽  
2020 ◽  
Vol 33 (13) ◽  
pp. 108533
Author(s):  
Paul van den Berk ◽  
Cesare Lancini ◽  
Carlos Company ◽  
Michela Serresi ◽  
Maria Pilar Sanchez-Bailon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Leukemia Cells ◽  
Genome Integrity ◽  
Hematopoietic Stem

scholarly journals USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells

2020 ◽  
Author(s):  
Paul van den Berk ◽  
Cesare Lancini ◽  
Carlos Company ◽  
Michela Serresi ◽  
Danielle Hulsman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Leukemia Cells ◽  
Genome Integrity ◽  
Hematopoietic Stem

Leukemia cells impair normal hematopoiesis and induce functionally loss of hematopoietic stem cells through immune cells and inflammation

2018 ◽  
Vol 65 ◽  
pp. 49-54 ◽  
Author(s):  
Ping Cui ◽  
Yuhua Zhang ◽  
Maoxiang Cui ◽  
Zhihong Li ◽  
Guang Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Immune Cells ◽  
Leukemia Cells ◽  
Hematopoietic Stem

Human Hematopoietic Stem Cells and Leukemic Cells Form Cadherin-Catenin Based Junctional Complexes with Mesenchymal Stromal Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1367-1367 ◽  
Author(s):  
Patrick Wuchter ◽  
Rainer Saffrich ◽  
Wolfgang Wagner ◽  
Frederik Wein ◽  
Mario Stephan Schubert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Leukemia Cells ◽  
Feeder Layer ◽  
Hematopoietic Stem ◽  
Knock Down ◽  
Junctional Complexes

Abstract The interaction between human hematopoietic stem cells (HSC) and their niche plays a key role in regulating maintenance of “stemness” and differentiation. We have demonstrated that a feeder layer of human mesenchymal stromal cells (MSC) can serve as a surrogate model for the niche for human HSC. We could also show, MSC are intimately connected to one another by a novel kind of adhering junction, consisting of villiformto-vermiform cell projections (processus adhaerentes). With this background, we have analyzed the intercellular junctional complexes between HSC and MSC. In comparison, we also studied the cell-cell contacts between leukemia cells (LC) and MSC. MSC were derived from bone marrow aspirates from healthy voluntary donors. HSC were isolated from umbilical cord blood. Leukemia cells that were CD34+ were obtained from bone marrow aspirates from patients suffering from acute myeloid leukemia at the time point of initial diagnosis. After 24–48 hours of co-cultivation, we stained the cellular contacts with a panel of antibodies specific for various components of tight, gap and adherens junctions. Using advanced confocal laser scanning microscopy in combination with deconvolution and volume rendering software, we were able to produce 3D-images of intercellular junctions between HSC/MSC as well as between LC/MSC. To examine the specific function of N-cadherin, we analyzed the effect of siRNA knock down of N-cadherin in MSC upon co-cultures of HSC and MSC. Intercellular connections between HSC and MSC are mainly characterized by podia formation of the HSC linking to the adjacent MSC. At the intimate contact zone to the MSC, we have identified the cytoplasmic plaque proteins alpha- and beta-catenin, co-localized with the transmembrane glycoprotein N-cadherin. Additionally, we compared these findings with a similar setting consisting of human LC co-cultured with feeder-layer of MSC. Our results demonstrated that in comparison to HSC, the proportion of leukemia cells adherent to the feeder-layer is significantly lower and podia formation is less frequent (ratio 1:3). However, the mechanism of adhesion through cadherin-catenin-complex has remained the same. At a functional level, we found that siRNA knock down of N-cadherin in MSC resulted in decreased adhesion of HSC to MSC and in a reduction of cell divisions of HSC. These results confirm that direct cellular contact via N-cadherin-based junctions is essential for homing and adhesion of HSC to the cellular niche and subsequently for the regulation of self-renewal versus differentiation in HSC.

scholarly journals Abstract 971: PRMT5 modulates splicing for genome integrity and preserves proteostasis of hematopoietic stem cells

2019 ◽  
Author(s):  
Darren Qiancheng Tan ◽  
Ying Li ◽  
Chong Yang ◽  
Jia Li ◽  
Shi Hao Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Genome Integrity ◽  
Hematopoietic Stem

scholarly journals PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells

Cell Reports ◽  
2019 ◽  
Vol 26 (9) ◽  
pp. 2316-2328.e6 ◽  
Author(s):  
Darren Qiancheng Tan ◽  
Ying Li ◽  
Chong Yang ◽  
Jia Li ◽  
Shi Hao Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Genome Integrity ◽  
Hematopoietic Stem

scholarly journals Remodeling of Bone Marrow Niches and Roles of Exosomes in Leukemia

2021 ◽  
Vol 22 (4) ◽  
pp. 1881
Author(s):  
Takanori Yamaguchi ◽  
Eiji Kawamoto ◽  
Arong Gaowa ◽  
Eun Jeong Park ◽  
Motomu Shimaoka
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Chemotherapy Resistance ◽  
Leukemia Cell ◽  
Cell Communication ◽  
Leukemia Cells ◽  
Hematopoietic Stem ◽  
Functional Changes ◽  
Bone Marrow Niches

Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.

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