Publications related to Haematopoietic system

Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis

Freddy Radtke, Ute Koch, Jialin Zhang, Soufiane Boumahdi

Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined f ...

ELSEVIER2023

Inhibition of SRC-mediated integrin signaling in bone marrow niche enhances hematopoietic stem cell function

Jörg Hülsken

Interaction with microenvironmental factors is crucial for the regulation of hematopoietic stem cell (HSC) function. Stroma derived factor (SDF)-1 alpha supports HSCs in the quiescent state and is central to the homing of transplanted HSCs. Here, we show t ...

CELL PRESS2022

New approaches to uncover the minimally functional hematopoietic niche using the adipocytic differentiation axis: pharmacological modulation and adrenal niche induction

Frédérica Schyrr

Hematopoietic Stem and Progenitor Cells (HSPCs) reside in their niche, a structure that regulates the balance of cellular quiescence, self-renewal and commitment towards differentiated cells. This highly plastic niche is formed by several cellular players, ...

EPFL2022

Notch signaling promotes disease initiation and progression in murine chronic lymphocytic leukemia

Freddy Radtke, Ute Koch, Jessica Sordet, Nadine Fournier, Marianne Nkosi, Delphine Maude Tardivon, Mateusz Waldemar Antoszewski

NOTCH1 gain-of-function mutations are recurrent in B-cell chronic lymphocytic leukemia (B-CLL), where they are associated with accelerated disease progression and refractoriness to chemotherapy. The specific role of NOTCH1 in the development and progressio ...

AMER SOC HEMATOLOGY2021

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Mateusz Waldemar Antoszewski

Notch1 receptor signaling is essential for T cell fate specification and physiological thymic T lymphocyte development. Its dysregulation and oncogenic activation are detected in almost 80% of pediatric patients suffering from T cell acute lymphoblastic le ...

EPFL2021

The Periostin/Integrin-alpha v Axis Regulates the Size of Hematopoietic Stem Cell Pool in the Fetal Liver

Jörg Hülsken

We earlier showed that outside-in integrin signaling through POSTN-ITGAV interaction plays an important role in regulating adult he-matopoietic stem cell (HSC) quiescence. Here, we show that Itgav deletion results in increased frequency of phenotypic HSCs ...

2020

MarrowQuantAcross Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections

Olaia Maria Naveiras Torres-Quiroga, Olivier Burri, Rita Sarkis, Nicolas Kunz, Vasco Ledebur de Antas de Campos, Josefine Catharina Pedersen Tratwal, Frédérica Schyrr, Chiheb Boussema, Shanti Rojas-Sutterlin, Daniel Naveed Tavakol

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapi ...

2020

In Vivo Pre-Instructed HSCs Robustly Execute Asymmetric Cell Divisions In Vitro

Matthias Lütolf, Aline Roch, Mukul Girotra, Vincent Trachsel

Hematopoietic stem cells (HSCs) are responsible for life-long production of all mature blood cells. Under homeostasis, HSCs in their native bone marrow niches are believed to undergo asymmetric cell divisions (ACDs), with one daughter cell maintaining HSC ...

2020

Quantitative approaches to unravel bone marrow adipocyte site-specificity and its implication in hematopoiesis

Josefine Catharina Pedersen Tratwal

Over the last decade, bone marrow (BM) adipose tissue (BMAT) has emerged as a distinct adipose depot with unique metabolic properties and effects both in homeostasis and in the progression of disease. We provide a first comprehensive review of existing an ...

EPFL2020

The nuclear receptor corepressor NCoR1 regulates hematopoiesis and leukemogenesis in vivo

Johan Auwerx, Wei Zhang, Lulu Liu, Yao Zhang, Na Zhang

Enhanced understanding of normal and malignant hematopoiesis pathways should facilitate the development of effective clinical treatment strategies for hematopoietic malignancies. Nuclear receptor corepressor 1 (NCoR1) has been implicated in transcriptional ...

AMER SOC HEMATOLOGY2019

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

Johan Auwerx, Matthias Lütolf, Bart Deplancke, Carlos Canto Alvarez, Olaia Maria Naveiras Torres-Quiroga, Aurélien Laurent Jean-Charles Oggier, George Coukos, Dongryeol Ryu, Eija Riitta Pirinen, Loïc Tauzin, Pedro Romero, Vasco Ledebur de Antas de Campos, Mukul Girotra, Josefine Catharina Pedersen Tratwal, Nicola Vannini, Pernille Yde Rainer, Joanna Ratajczak, Vincent Trachsel, Sonja Giger, Shanti Rojas-Sutterlin, Gennady Nikitin, Yang Li, Federico Sizzano, Simone Ragusa, Yannick Lionel Yersin, Martin Ehrbar

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here w ...

CELL PRESS2019

Metabolic and microenvironmental strategies to accelerate hematopoietic recovery post-aplasia

Vasco Ledebur de Antas de Campos

The procedure-associated mortality rate of bone marrow transplantations (BMT) remains close to 25%. The BMT is therefore only indicated for life-threatening diseases, with no replacement of this technology to be expected in the foreseeable future. Modest i ...

EPFL2019

In vitro fate mapping of stem cell development at the single cell level

Vincent Trachsel

Hematopoietic stem cells (HSCs) are responsible for the continuous production of all blood cells. This unique ability has made it possible to successfully use HSCs in the clinical setting to remedy various blood disorders. However, despite six decades of r ...

EPFL2018

Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF(high) neutrophils

Etienne Meylan, Ferdinando Pucci, Julien Robert Rémi Faget

Bone marrow-derived myeloid cells can accumulate within tumors and foster cancer outgrowth. Local immune-neoplastic interactions have been intensively investigated, but the contribution of the systemic host environment to tumor growth remains poorly unders ...

American Association for the Advancement of Science2017

Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation

Jörg Hülsken, Zuzana Tatárová

Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation ...

Cell Press2017

T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNF alpha Expression and Empower Adoptive Cell Therapy for Solid Tumors

Melody Swartz

Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reprod ...

Amer Assoc Cancer Research2017

Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis

Jörg Hülsken, Albert Santamaria Martinez

Integrins play an important role in haematopoietic stem cell (HSC) maintenance in the bone marrow niche. Here, we demonstrate that Periostin (Postn) via interaction with Integrin-alpha v (Itgav) regulates HSC proliferation. Systemic deletion of Postn resul ...

Nature Publishing Group2016

Specification of haematopoietic stem cell fate via modulation of mitochondrial activity

Johan Auwerx, Matthias Lütolf, Aline Roch, Olaia Maria Naveiras Torres-Quiroga, Mukul Girotra, Nicola Vannini, Vasco Ledebur de Antas de Campos, Gennady Nikitin, Sonja Giger

Haematopoietic stem cells (HSCs) differ from their committed progeny by relying primarily on anaerobic glycolysis rather than mitochondrial oxidative phosphorylation for energy production. However, whether this change in the metabolic program is the cause ...

Nature Publishing Group2016

The chromatin remodeller Chd7 and the calcium ATPase Serca2 - adding new facets to the role of Notch in Hematopoiesis and T-ALL

Monique Coersmeyer

Project I: Chd7 Deficiency does not affect N1-driven T-ALL Induction and Maintenance nor impair Hematopoiesis Notch1 has been shown to be a key driver in pediatric T-cell acute lymphobastic leukemia (T-ALL). Previous work in the lab identified the chromati ...

EPFL2015

Deciphering Metabolic Regulation of Hematopoietic Stem Cell Fate

Mukul Girotra

Hematopoietic stem cells (HSCs) are responsible for life-long production of all mature blood cells. This unique characteristic makes them an ideal candidate for cell-based therapies to treat various hematological malignancies. Their extensive use in the cl ...

EPFL2015