scholarly journals In Lyl1-/- mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues

2020 ◽  
Author(s):  
Abid Hussain ◽  
Leila El Kebriti ◽  
Virginie Deleuze ◽  
Yaël Glasson ◽  
Nelly Pirot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Fat Tissue ◽  
Adipose Stem Cell ◽  
Adipose Tissues ◽  
Vascular Niche ◽  
Vascular Structures ◽  
Deficient Mice ◽  
Vascular Compartment

ABSTRACTLymphoblastic leukemia-derived sequence 1 (Lyl1) encodes a hematopoietic- and endothelial-specific transcriptional factor. Lyl1-deficient mice are viable, but they display mild hematopoietic and vascular defects. Here, we report that young Lyl1-/- mice exhibit transient obesity associated with general expansion of adipose tissues and unrelated to food intake. The increased fat tissue development in Lyl1-/- mice resulted from an earlier adipocyte differentiation of adipose stem cells (ASCs) through non-cell autonomous mechanisms. Specifically, we found that in Lyl1-/- mice, the vascular structures of adipose tissues are unstable, more prone to angiogenesis and, consequently, cannot maintain adipose progenitors in the niche vessel wall. Together, our data show that in Lyl1-/- mice, the impaired vascular compartment of the adipose niche promotes uncontrolled ASC activation and differentiation, leading to early adipocyte expansion and premature depletion of ASCs. Our study highlights the major structural role of the adipose tissue vascular niche in coordinating stem cell self-renewal and differentiation into adipocytes.

scholarly journals The Dynamic Interface Between the Bone Marrow Vascular Niche and Hematopoietic Stem Cells in Myeloid Malignancy

2021 ◽  
Vol 9 ◽  
Author(s):  
Laura Mosteo ◽  
Joanna Storer ◽  
Kiran Batta ◽  
Emma J. Searle ◽  
Delfim Duarte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Vascular Niche ◽  
Dynamic Interface ◽  
Bone Marrow Vascular Niche ◽  
Bidirectional Interactions ◽  
Vascular Compartment

Hematopoietic stem cells interact with bone marrow niches, including highly specialized blood vessels. Recent studies have revealed the phenotypic and functional heterogeneity of bone marrow endothelial cells. This has facilitated the analysis of the vascular microenvironment in steady state and malignant hematopoiesis. In this review, we provide an overview of the bone marrow microenvironment, focusing on refined analyses of the marrow vascular compartment performed in mouse studies. We also discuss the emerging role of the vascular niche in “inflamm-aging” and clonal hematopoiesis, and how the endothelial microenvironment influences, supports and interacts with hematopoietic cells in acute myeloid leukemia and myelodysplastic syndromes, as exemplar states of malignant myelopoiesis. Finally, we provide an overview of strategies for modulating these bidirectional interactions to therapeutic effect in myeloid malignancies.

scholarly journals Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2486-2496 ◽  
Author(s):  
Nathalie Dhédin ◽  
Anne Huynh ◽  
Sébastien Maury ◽  
Reza Tabrizi ◽  
Kheira Beldjord ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Key Points ◽  
First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

The Role of the Donor in the Repair of the Marrow Vascular Niche Following Hematopoietic Stem Cell Transplant

Stem Cells ◽  
2007 ◽  
Vol 25 (11) ◽  
pp. 2945-2955 ◽  
Author(s):  
William B. Slayton ◽  
Xiao-Miao Li ◽  
Jason Butler ◽  
Steven M. Guthrie ◽  
Marda L. Jorgensen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Vascular Niche

scholarly journals LYL1 activity is required for the maturation of newly formed blood vessels in adulthood

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5270-5279 ◽  
Author(s):  
Nelly Pirot ◽  
Virginie Deleuze ◽  
Rawan El-Hajj ◽  
Christiane Dohet ◽  
Fred Sablitzky ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Wild Type ◽  
Postnatal Maturation ◽  
Helix Loop Helix ◽  
Hematopoietic Reconstitution ◽  
Vascular Structures ◽  
Angiopoietin 2 ◽  
Aortic Explants ◽  
Deficient Mice

Abstract The 2 related basic helix loop helix genes, LYL1 and TAL-1 are active in hematopoietic and endothelial lineages. While Tal-1 is essential for both hematopoietic and vascular development, the role of Lyl1 appears to be distinct as deficient mice are viable and display modest hematopoietic defects. Here, we reveal a role for Lyl1 as a major regulator of adult neovascularization. Tumors implanted into Lyl1-deficient mice showed higher proliferation and angiogenesis, as evidenced by enlarged lumens, reduced pericyte coverage and increased permeability, compared with wild type littermates. Of note, Lyl1-deficient tumor vessels exhibited an up-regulation of Tal-1, the VE-Cadherin target gene, as well as Angiopoietin-2, 3 major actors in angiogenesis. Hematopoietic reconstitution experiments demonstrated that this sustained tumor angiogenesis was of endothelial origin. Moreover, the angiogenic phenotype observed in the absence of Lyl1 function was not tumor-restricted as microvessels forming in Matrigel or originating from aortic explants were also more numerous and larger than their wild-type counterparts. Finally, LYL1 depletion in human endothelial cells revealed that LYL1 controls the expression of molecules involved in the stabilization of vascular structures. Together, our data show a role for LYL1 in the postnatal maturation of newly formed blood vessels.

scholarly journals Prognostic Role of Minimal Residual Disease before and after Hematopoietic Stem Cell Transplantation in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1413-1413
Author(s):  
Bartolomeo Rossi ◽  
Mimma Campeggio ◽  
Elisa Magrin ◽  
Marco Zecca ◽  
Laura Rubert ◽  
...  
Keyword(s):  
Stem Cell ◽  
Poor Prognosis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Good Prognosis ◽  
Prognostic Role ◽  
Hematopoietic Stem ◽  
Before And After ◽  
Minimal Residual

Abstract Background and Objectives Currently, more than 80% of children with acute lymphoblastic leukemia (ALL) can be cured through intensive and risk-adapted chemotherapy protocols. Allogeneic hematopoietic stem cell transplantation (HSCT) is considered beneficial for approximately 10% of the patients who are at very-high risk at frontline therapy and for the majority of patients after relapse. In this retrospective study, we aimed to assess the prognostic role of minimal residual disease (MRD) before HSCT and at different time points after transplantation in children with ALL. Patients and Methods We analyzed 64 pediatric ALL patients given HSCT: 22/64 were in first complete remission (1CR) and 42/64 in second complete remission (2CR). Genomic DNA was obtained from bone marrow aspirates collected at diagnosis/relapse, before HSCT (pre-HSCT) and at the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). MRD was measured by quantitative real-time PCR assays based on patient-specific junctional regions and interpreted according to the EuroMRD guidelines. The association between MRD and survival was assessed by chi-square test. Results All evaluated patients were analyzed for MRD before transplantation (pre-HSCT). MRD was negative in 26/64 patients and positive in 38/64 patients. As for cases with positive MRD, 17/38 showed MRD levels ≥1x10-3 and 21/38 <1x10-3. Any detectable MRD positivity at pre-HSCT was significantly associated with a poor prognosis: 28/38 patients with positive MRD are dead, whereas 22/26 with negative MRD are alive in CR (P < 0.001). Among the 42 patients in 2CR, 14/42 had negative pre-HSCT MRD and 28/42 were MRD positive. The negativity of MRD before transplantation was found to be significantly associated with a good prognosis: 13/14 patients with negative MRD are alive in CR, while 23/28 with positive MRD are dead (p < 0.001). Post-HSCT1 MRD was analyzed in 53 patients: 17/53 were MRD positive and 36/53 were MRD negative. Based on MRD status, the prognosis was significantly different: 26/36 patients with negative post-HSCT1 MRD are alive in CR, whereas 14/17 of patients with positive MRD are dead (P < 0.001). Post-HSCT3 MRD was assessed in 41 patients and 19/41 were found positive. Persistence of MRD was associated with a poor prognosis also at this time-point (P = 0.001). Conclusions These results confirm that MRD assessment has a critical role both before and after transplantation. Negative MRD before transplantation is strongly associated with a good prognosis, particularly in 2CR patients. Since persistence of MRD after HSCT is significantly associated with a worse outcome, these patients could benefit from early discontinuation of immunosuppression, adoptive T-cell therapy and use of new drugs. Disclosures No relevant conflicts of interest to declare.

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