Simon Haas

Simon Haas
German Cancer Research Center | DKFZ · Division of Stem Cells and Cancer & HI-STEM gGmbH

About

91
Publications
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Introduction
Simon Haas is a research group leader at group leader at the Berlin Institute of Health (BIH), the Charité university medicine, and the Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center (MDC) in Berlin and HI-STEM and the German Cancer Research Center (DKFZ) in Heidelberg.

Publications

Publications (91)
Article
Infections are associated with extensive platelet consumption, representing a high risk for health. However, the mechanism coordinating the rapid regeneration of the platelet pool during such stress conditions remains unclear. Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed pr...
Article
Full-text available
Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory mechanisms. Here, we comprehensively map myeloid proge...
Article
Full-text available
Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell...
Article
Blood and immune cells derive from multipotent hematopoietic stem cells (HSCs). Classically, stem and progenitor populations have been considered discrete homogeneous populations. However, recent technological advances have revealed significant HSC heterogeneity, with evidence for early HSC lineage segregation and the presence of lineage-biased HSC...
Article
Full-text available
The bone marrow constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular and spatial organization remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular, cellular and spatial composition of distinct bone marrow niches. This al...
Article
In a recent Nature Medicine study, Zeng and colleagues integrate both genomic and stem cell models of acute myeloid leukemia (AML) by deconvoluting cellular hierarchies of more than 1,000 AML samples. This work introduces a framework capable of predicting drug responses to targeted therapies in future clinical trials.
Preprint
Full-text available
Inter-patient variability and the similarity of healthy and leukemic stem cells have impeded the characterization of leukemic stem cells (LSCs) in acute myeloid leukemia (AML), and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 A...
Article
Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functiona...
Article
Full-text available
Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell-mediated immunosurveillance b...
Article
Full-text available
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell po...
Article
Infections are a key source of stress to the hematopoietic system. While infections consume short-lived innate immune cells, their recovery depends on quiescent hematopoietic stem cells (HSCs) with long-term self-renewal capacity. Both chronic inflammatory stress and bacterial infections compromise competitive HSC capacity and cause bone marrow fai...
Article
This year’s Gairdner Foundation Award for Biomedical Research is awarded to John Dick for the discovery of leukemic stem cells and the hierarchical organization of acute myeloid leukemias. His work laid the foundation for the cancer stem cell model with numerous clinical implications for hematopoietic malignancies and solid tumors.
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Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps of huma...
Article
Hematopoietic stem cells (HSCs) continuously generate blood and immune cells, including T cells and antigen-presenting cells (APCs). Antigen presentation by APCs to CD4+ helper T cells constitutes the central process in the orchestration of adaptive immune responses. While T cells play a vital role in regulating stem cell biology, stem cells are no...
Article
Decline in hematopoietic stem cell (HSC) function with age underlies limited health span of our blood and immune systems. In order to preserve health into older age, it is necessary to understand the nature and timing of initiating events that cause HSC aging. By performing a cross-sectional study in mice, we discover that hallmarks of aging in HSC...
Preprint
Full-text available
Single-cell genomics has transformed our understanding of complex cellular systems. However, excessive costs and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high content single-cell proteo-genomic reference maps of human blood an...
Article
Full-text available
Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance an...
Article
To date, multiple myeloma (MM) remains an incurable disease with only a minor fraction of patients experiencing long-term remission (LTR) over 7 years after a single therapy line. Myeloma cells strongly depend on the interaction with their bone marrow microenvironment (BMME), but the molecular and cellular adaptations of the BMME to active MM disea...
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The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chrom...
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Purpose of Review Hematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells. This review provides an overview of how single-cell (multi)-omic approaches have recently advanced our understanding of healthy hematopoiesis, hematological malignancies, and the stem cell niche. Recent Findings Single-cell tech...
Preprint
Full-text available
Hematopoietic stem cells (HSCs) are canonically defined by their capacity to maintain the HSC pool via self-renewal divisions. However, accumulating evidence suggests that HSC function is instead preserved by sustaining long-term quiescence. Here, we study the kinetics of HSC recovery in mice, following an inflammatory challenge that induces HSCs t...
Article
Full-text available
5-Methylcytosine is a stable epigenetic modification, whose remodeling at specific CpG residues appears integral to the process of enforcing lineage-restricted gene expression. In our previously generated DNA methylation map of the entire murine hematopoietic system we have observed that DNA methylation programming appears to be both progressive an...
Article
Inflammation has a great impact on an organism. In order to protect the hematopoietic system from exhaustion during pathogenic insult, heterogeneity in metabolic activity, gene expression patterns, and responsiveness to cytokines such as interferons (IFN) have been revealed. Yet, how this diversity in the system is generated and maintained remains...
Preprint
Hematopoietic stem cells (HSCs) are responsible for lifelong maintenance and regeneration of the blood system. With aging, loss of HSC function is a major contributor to decline in overall hematopoietic function, leading to increased rate of infection, poor vaccination response, clonal hematopoiesis, and increased risk of hematologic malignancies....
Article
Blood production is essential to maintain human health, and even small perturbations in hematopoiesis can cause disease. Hematopoiesis has therefore been the focus of much research for many years. Experiments determining the lineage potentials of hematopoietic stem and progenitor cells (HSPCs) in vitro and after transplantation revealed a hierarchy...
Article
The coordinated differentiation of hematopoietic stem and progenitor cells (HSPCs) into the various mature blood cell types is responsible for sustaining blood and immune system homeostasis. The cell fate decisions underlying this important biological process are made at the level of single cells. Methods to trace the fate of single cells are there...
Preprint
Full-text available
The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chrom...
Preprint
Full-text available
Despite important advances in the treatment of breast cancer, the 5-year survival rate for patients with distant metastasis remains less than 30%. Metastasis is a complex, multi-step process beginning with local invasion and ending with the outgrowth of systemically disseminated cells into actively proliferating metastases that ultimately cause the...
Conference Paper
Although the survival of patients diagnosed with breast cancer has greatly improved over the last decades, the metastatic stage of the disease still remains incurable. Blood circulating tumor cells (CTCs) are assumed to be the source for metastatic onset and the enumeration of CTCs has already proven its prognostic value for survival in metastatic...
Article
Purpose of review: The bone marrow is home to hematopoietic stem cells responsible for lifelong blood production, alongside mesenchymal stem cells required for skeletal regeneration. In the bone marrow, a unique combination of signals derived from a multitude of cell types results in the establishment of so-called niches that regulate stem-cell ma...
Article
Recent advances in single cell transcriptome analyses have resulted in the derivation of new models to describe the hierarchical organization of the mammalian hematopoietic system. While such an approach appears to be effective at discerning the trajectory of differentiation from hematopoietic stem cells (HSCs) to a given mature lineage, it remains...
Article
Elevated levels of inflammation have been previously linked to both inherited and acquired bone marrow failure (BMF) syndromes, as well as to normal aging, suggesting a role in the etiology of these conditions. One potential explanation for this phenomenon is that repeated inflammation can promote the suppression of hematopoietic stem cell (HSC) fu...
Preprint
Full-text available
The bone marrow (BM) constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular composition and the spatial organization into distinct ‘niches’ remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular and cellular composition of t...
Preprint
Full-text available
The step-wise acquisition of genetic abnormalities in cancer is thought to represent a major driver of disease initiation, relapse and therapy resistance. Acute myeloid leukemia (AML) represents a prime example of an aggressive cancer that develops in a multi-step manner from multipotent hematopoietic progenitors via pre-leukemic intermediates to l...
Article
Coordinated interaction of many cell types is required to facilitate hematopoietic and mesenchymal stem cell maintenance and differentiation in the bone marrow. However, the molecular factors and cell types involved in this complex interplay remain poorly understood. Here we developed a combined single cell and spatial transcriptomics approach to a...
Article
Specific protection mechanisms are required to safeguard stem cell integrity. In a recent issue of Cell, Wu et al. (2018) show that stem cells are equipped with high intrinsic expression of interferon-stimulated genes (ISGs) but remain refractory to acute interferon signaling. This protects stem cells from viral infection.
Article
Mature blood and immune cells show broad inter- and intra-cell type-specific heterogeneity with respect to metabolic activity, gene expression patterns, differentiation capacity and responsiveness to cytokines such as interferons (IFNs). This diversity is of crucial importance to maintain the capacity of the immune system to appropriately react to...
Article
The hematopoietic system is responsible for transporting oxygen and nutrients, fighting infections, and repairing tissue damage. Hematopoietic system dysfunction therefore causes a range of serious health consequences. Lifelong hematopoiesis is maintained by repopulating multipotent hematopoietic stem cells (HSCs) that replenish shorter-lived, matu...
Article
Full-text available
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed...
Article
Full-text available
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substan...
Article
In the bone marrow (BM), endothelial cells (ECs) are a major component of the hematopoietic stem cell (HSC) vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha (IFNα). In the BM, IF...
Article
An often-cited defining property of hematopoietic stem cells (HSCs) is their extensive or unlimited in vivo self-renewal capacity. We have recently described a novel mouse disease model forFanconi anemia, in which serial challenge with pro-inflammatory agonists that mimic infection, such aspolyinosinic:polycytidylic acid (pI:C), results in HSC attr...
Article
Epigenetic drugs are currently used for the treatment of several hematologic malignancies, but their mechanism of action remains poorly understood. By using a previously described reporter cell line for epigenetic reactivation of the DAPK1 locus, we have shown that epigenetic treatment causes transcription from uncharacterized intronic transcriptio...
Article
Full-text available
In the bone marrow, endothelial cells are a major component of the hematopoietic stem cell vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha. In the bone marrow, interferon alpha...
Article
Full-text available
During homeostasis, hematopoietic stem cells (HSCs) are mostly kept in quiescence with only minor contribution to steady-state hematopoiesis. However, in stress situations such as infection, chemotherapy, or transplantation, HSCs are forced to proliferate and rapidly regenerate compromised hematopoietic cells. Little is known about the processes re...
Article
Full-text available
Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, lead...
Data
Table S1. Number of cDNA Sequenced Fragments per Sample per Gene, Related to Figure 2 Each column of the matrix represents a sample and each row represents one gene. The matrix is filled with the number of reads that were tabulated to each gene based on the genomic coordinates of both the read alignments to the reference genome and the annotation...