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Fulfilling the Promise: Pluripotent Stem Cells as Models for Human Blood Development and Disease

Generation of self-renewing hematopoietic stem cells (HSCs) from human pluripotent stem cells (PSCs) for transplantation and disease modeling has been a long-standing goal in the field, but has been hampered by the difficulty in differentiating bona fide HSCs in culture. In recent years there has been tremendous progress in the field, and investigators have been able to define the developmental cues to direct mesodermal differentiation to definitive HSC fate rather than defaulting to embryonic type progenitors. These studies have been further fueled by the advances in single cell transcriptomic technologies, which has made it possible to compare in vitro HSC development to human HSCs developing in vivo. Advances in this area of research will be highlighted in this session.

Co-Chairs:

Elizabeth W. Ng, MD
Kansas City Cancer Center
Overland Park, KS

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Icahn School of Medicine at Mount Sinai
New York, NY

Speakers:

Elizabeth W. Ng, MD
Kansas City Cancer Center
Overland Park, KS
Hematopoietic Stem Cell Development from Human Pluripotent Stem Cells

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Icahn School of Medicine at Mount Sinai
New York, NY
Modeling Blood Disorders Using Human Pluripotent Stem Cells

Biology Underlying Disparities in Lymphoid Malignancies

Significant disparities in outcomes have been described for several lymphoma subtypes, most notably related to race and HIV status. Although socioeconomic factors often play a role, new approaches are needed to determine whether distinct pathogenic mechanisms underlie such disparities. The modern era has been marked by major advances in understanding lymphoma pathobiology, but populations affected by disparities are woefully under-represented in most of these pivotal studies. This session will highlight recent, innovative work dedicated to closing this knowledge gap and identifying molecular targets for improving outcomes in vulnerable populations.

Co-Chairs:

Christopher R. Flowers, MD,MSc
The University of Texas MD Anderson Cancer Center
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Wendy Cozen, DO, MPH
UCI, School of Medicine
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Speakers:

Christopher R. Flowers, MD, MS
The University of Texas MD Anderson Cancer Center
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Tumor Sequencing to Investigate Disparities in Lymphoma

Wendy Cozen, DO, MPH
UCI, School of Medicine
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Tumor Microenvironment Profiling to Investigate Disparities in Hodgkin Lymphoma and Multiple Myeloma

Inflammation as a Regulator of Hematopoietic Homeostasis in Disease and Clonal Selection

Hematopoietic stem and progenitor cells (HSPCs) are responsible for integrating inflammatory cues into cellular responses and establishing a demand-adapted axis between peripheral stresses and hematopoietic responses in the bone marrow. This session will describe how the pro-inflammatory environment/response and systemic inflammation act on and subsequently shape HSPC and hematopoietic homeostasis.

Co-Chairs:

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Kumamoto University
Kumamoto City, Japan

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University of California San Francisco
San Francisco, CA

Speakers:

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Kumamoto University
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Inflammation As a Regulator of Hematopoietic Homeostasis in Disease

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University of California San Francisco
San Francisco, CA
Inflammation As a Regulator of Hematopoietic Homeostasis in Clonal Selection

Iron at the Crossroads Between Erythropoiesis and Megakaryopoiesis

This session will highlight the importance of iron balance for a healthy and effective erythropoiesis and thrombopoiesis. All mammalian cells rely on iron for normal functioning, with the erythropoietic compartment consuming the majority given the high iron requirements for hemoglobin synthesis. Recent evidence on the crosstalk between erythropoiesis and iron metabolism shed light on the consequences of insufficient as well as excess iron and heme on erythroid lineage proliferation and differentiation. In this session, the contribution of heme and iron excess to ineffective erythropoiesis will be described, with a focus on erythroid cell trajectories during differentiation, metabolic shifts, and erythroid cell-macrophage interaction within erythroblastic islands (EBIs). The session will also describe the role iron plays in other hematopoietic processes, including megakaryopoiesis and platelet formation.

Co-Chairs:

Janis L. Abkowitz, MD
University of Washington
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Radek C. Skoda, MD
University Hospital Basel
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Speakers:

Janis L. Abkowitz, MD
University of Washington
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Role of Heme and Iron in Effective and Ineffective Erythropoiesis

Radek C. Skoda, MD
University Hospital Basel
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Impact of Iron Availability on Megakaryopoiesis

Phylogenetic Reconstruction of Hematopoiesis

Hematopoiesis is a complex and highly regulated process that has been increasingly understood through advances in genetics, epigenetics, and single-cell genomics technologies. Recent work has focused on increasingly nuanced and detailed phylogenies of hematopoietic cells in normal and aged individuals, and multidimensional understanding of phylogenetic trees of stem cells, progenitors, and mature progeny. Genomics, epigenetics, advanced computational analyses, large scale datasets, and single-cell approaches are all integral in this effort. This session will present some of the latest advances in the field and serve to educate the audience of how these may inform our understanding of physiological and pathological mechanisms in hematopoiesis.

Co-Chairs:

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Wellcome Sanger Institute
Hinxton, United Kingdom

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Stanford University
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Speakers:

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Wellcome Sanger Institute
Hinxton, United Kingdom
Incorporating Genetic and Epigenetic Marks in Phylogenetic Reconstruction of Blood Cells

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Stanford University
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Novel Single-Cell Genomics Technologies to Reconstruct Phylogenetics of Human Blood Cells