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JOINT Session - Cell Competition and Clonal Hematopoiesis

PhD Trainee
Sponsor: Scientific Committee on Hematopoiesis||Scientific Committee on Stem Cells and Regenerative Medicine
Program: Scientific Program
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, MDS, Clinical Practice (Health Services and Quality), Genetic Disorders, genomics, hematopoiesis, Chronic Myeloid Malignancies, Diseases, immune mechanism, metabolism, Biological Processes, Myeloid Malignancies, multi-systemic interactions
Sunday, December 11, 2022: 9:30 AM-11:05 AM
New Orleans Theater AB (Ernest N. Morial Convention Center)

Description:
This session will focus on the concept of cell competition, the process by which interactions between cells with different fitness levels within a tissue enables clonal emergence and dominance. It will provide the attendees with a thorough overview of cell competition and how this alters tissue homeostasis in a range of biological models. It will also discuss how cell competition contributes to clonal hematopoiesis in pre-malignant and malignant hematopoiesis. Finally, it will discuss how interactions of hematopoietic stem and progenitor cells with hematopoietic niches are dysregulated to favor clonal hematopoiesis. 

 

Dr. Laura Johnston will introduce the concept of cell competition, providing a brief history of its study in invertebrate and vertebrate genetic models. Dr. Johnston will present an overview of the basic regulatory mechanisms that operate in different contexts of cell competition and super-competition, and discuss how competitive cell-cell interactions affect tissue homeostasis during animal development, in cancer and during aging. 

 

Dr. Alejo Rodriguez-Fraticelli will present results related to the clonal analysis of Dnmt3a-mutant premalignant hematopoiesis. Using conventional and single-cell lineage tracing approaches, Dr. Fraticelli is identifying the functional and transcriptional variation between different mutant Dnmt3a hematopoietic stem cell (HSC) clones. He will also present new evidence regarding the interactions between age-related HSC and Dnmt3a mutations, which clarifies the mechanism that Dnmt3a mutant cells use to compete and expand in detriment of the normal hematopoietic compartment.   

 

Dr. Ann Mullally will describe the early pathogenesis of myeloproliferative neoplasms (MPN), from acquisition of an MPN phenotypic driver mutation, through the clonal expansion of MPN stem cells, to the development of overt MPN. She will also discuss how recent single-cell approaches have advanced the understanding of the mechanisms underlying clonal dominance and myeloid transformation as it pertains to MPN. Finally, Dr. Mullally will highlight the potential to exploit these new biological insights for therapeutic gain in MPN. 

 

Dr. Dominique Bonnet will discuss how advanced imaging technologies have enabled the study of how cell competition affects interactions with hematopoietic niches. She will describe the clonal dynamics underlying the responses of human hematopoietic stem/progenitor cells (HSPCs) to inflammatory signals in lungs and bone marrow using the immunodeficient mouse xenotransplant repopulating assay. Dr. Dominique Bonnet will also present some preliminary data on the effect of Tet2 mutations in clonal competition with wild-type HSPCs under homeostasis and during inflammation.

Chair:
Louise E. Purton, PhD, St Vincent’s Institute of Medical Research
Disclosures:
No relevant conflicts of interest to declare.
This session will focus on the concept of cell competition, the process by which interactions between cells with different fitness levels within a tissue enables clonal emergence and dominance. It will provide the attendees with a thorough overview of cell competition and how this alters tissue homeostasis in a range of biological models. It will also discuss how cell competition contributes to clonal hematopoiesis in pre-malignant and malignant hematopoiesis. Finally, it will discuss how interactions of hematopoietic stem and progenitor cells with hematopoietic niches are dysregulated to favor clonal hematopoiesis. 

 

Dr. Laura Johnston will introduce the concept of cell competition, providing a brief history of its study in invertebrate and vertebrate genetic models. Dr. Johnston will present an overview of the basic regulatory mechanisms that operate in different contexts of cell competition and super-competition, and discuss how competitive cell-cell interactions affect tissue homeostasis during animal development, in cancer and during aging. 

 

Dr. Alejo Rodriguez-Fraticelli will present results related to the clonal analysis of Dnmt3a-mutant premalignant hematopoiesis. Using conventional and single-cell lineage tracing approaches, Dr. Fraticelli is identifying the functional and transcriptional variation between different mutant Dnmt3a hematopoietic stem cell (HSC) clones. He will also present new evidence regarding the interactions between age-related HSC and Dnmt3a mutations, which clarifies the mechanism that Dnmt3a mutant cells use to compete and expand in detriment of the normal hematopoietic compartment.   

 

Dr. Ann Mullally will describe the early pathogenesis of myeloproliferative neoplasms (MPN), from acquisition of an MPN phenotypic driver mutation, through the clonal expansion of MPN stem cells, to the development of overt MPN. She will also discuss how recent single-cell approaches have advanced the understanding of the mechanisms underlying clonal dominance and myeloid transformation as it pertains to MPN. Finally, Dr. Mullally will highlight the potential to exploit these new biological insights for therapeutic gain in MPN. 

 

Dr. Dominique Bonnet will discuss how advanced imaging technologies have enabled the study of how cell competition affects interactions with hematopoietic niches. She will describe the clonal dynamics underlying the responses of human hematopoietic stem/progenitor cells (HSPCs) to inflammatory signals in lungs and bone marrow using the immunodeficient mouse xenotransplant repopulating assay. Dr. Dominique Bonnet will also present some preliminary data on the effect of Tet2 mutations in clonal competition with wild-type HSPCs under homeostasis and during inflammation.

Laura A. Johnston

Vagelos College of Physicians and Surgeons, Columbia University, New York, NY

Alejo E. Rodriguez-Fraticelli, PhD

IRB Barcelona, Barcelona, Spain

Ann Mullally, MD

Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Domique Bonnet, PhD

1 Midland Road, Francis Crick Institute, London, ENG, United Kingdom

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