Kellie R. Machlus
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View article: CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias
CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias Open
Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem-cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem-c…
View article: Induction of Moderate DNA Damage Enhances Megakaryopoiesis and Platelet Production
Induction of Moderate DNA Damage Enhances Megakaryopoiesis and Platelet Production Open
Megakaryocytes (MKs) are large, hematopoietic cells with a polyploid, multi-lobulated nucleus. While DNA replication in MKs (endomitosis) is well studied, limited investigations have examined the impact of DNA instability on megakaryopoies…
View article: Induction of Moderate DNA Damage Enhances Megakaryopoiesis and Platelet Production
Induction of Moderate DNA Damage Enhances Megakaryopoiesis and Platelet Production Open
A common side effect of poly-ADP ribose polymerase (PARP) inhibitors is low platelet counts, or thrombocytopenia, presumably mediated through platelet progenitors, megakaryocytes (MKs). MKs are large, hematopoietic cells with a polyploid, …
View article: DNMT3A regulates murine megakaryocyte-biased hematopoietic stem cell fate decisions
DNMT3A regulates murine megakaryocyte-biased hematopoietic stem cell fate decisions Open
Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to…
View article: CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias
CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias Open
Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem c…
View article: Inhibition of RhoA-mediated secretory autophagy in megakaryocytes mitigates myelofibrosis in mice
Inhibition of RhoA-mediated secretory autophagy in megakaryocytes mitigates myelofibrosis in mice Open
Megakaryocytes (MKs) are large, polyploid cells that contribute to bone marrow homeostasis through the secretion of cytokines such as transforming growth factor β1 (TGFβ1). During neoplastic transformation, immature MKs accumulate in the b…
View article: Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation
Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation Open
Platelets are essential for hemostasis, and thrombocytopenia is a major clinical problem. Megakaryocytes (MKs) generate platelets by extending long processes, proplatelets, into sinusoidal blood vessels. However, very little is known about…
View article: Cell cycle–dependent centrosome clustering precedes proplatelet formation
Cell cycle–dependent centrosome clustering precedes proplatelet formation Open
Platelet-producing megakaryocytes (MKs) primarily reside in the bone marrow, where they duplicate their DNA content with each cell cycle resulting in polyploid cells with an intricate demarcation membrane system. While key elements of the …
View article: SARS-CoV-2 infection modifies the transcriptome of the megakaryocytes in the bone marrow
SARS-CoV-2 infection modifies the transcriptome of the megakaryocytes in the bone marrow Open
Megakaryocytes (MKs), integral to platelet production, predominantly reside in the bone marrow (BM) and undergo regulated fragmentation within sinusoid vessels to release platelets into the bloodstream. Inflammatory states and infections i…
View article: The Quantitative Impact of Warfarin Versus Factor Xa Inhibitors on Anticoagulation Profiles in Patients With Peripheral Artery Disease Post-Revascularization
The Quantitative Impact of Warfarin Versus Factor Xa Inhibitors on Anticoagulation Profiles in Patients With Peripheral Artery Disease Post-Revascularization Open
View article: Evidence for a cytoplasmic proplatelet promoting factor that triggers platelet production
Evidence for a cytoplasmic proplatelet promoting factor that triggers platelet production Open
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View article: The many faces of the megakaryocytes and their biological implications
The many faces of the megakaryocytes and their biological implications Open
Purpose of review Single-cell RNA sequencing studies have revealed transcriptional heterogeneity within the megakaryocytic lineage and the identified unique subsets. In this review, we discuss the functional and phenotypic plasticity of th…
View article: The bone marrow is the primary site of thrombopoiesis
The bone marrow is the primary site of thrombopoiesis Open
Megakaryocytes (MKs) generate thousands of platelets over their lifespan. The roles of platelets in infection and inflammation has guided an interest to the study of extramedullary thrombopoiesis and therefore MKs have been increasingly re…
View article: PB0378 DNA Damage Accumulation in Polyploid Megakaryocytes: Investigating the Impact of Poly (ADP-ribose) Polymerase (PARP) Inhibitors
PB0378 DNA Damage Accumulation in Polyploid Megakaryocytes: Investigating the Impact of Poly (ADP-ribose) Polymerase (PARP) Inhibitors Open
platelets and dyserythropoietic features caused by mutations in the transcription factor GATA binding protein 1 (GATA1).We have established an immunofluorescence-based method for phenotyping platelets on the blood smear, which we have vali…
View article: PB0379 Study of Megakaryocytes in Systemic Lupus Erythematosus
PB0379 Study of Megakaryocytes in Systemic Lupus Erythematosus Open
View article: Dynamic actin/septin network in megakaryocytes co-ordinates proplatelet elaboration
Dynamic actin/septin network in megakaryocytes co-ordinates proplatelet elaboration Open
Megakaryocytes (MKs) undergo extensive cytoskeletal rearrangements as they give rise to platelets. While cortical microtubule sliding has been implicated in proplatelet formation, the role of the actin cytoskeleton in proplatelet elongatio…
View article: Peripheral megakaryocytes sound the alarm in COVID-19
Peripheral megakaryocytes sound the alarm in COVID-19 Open
View article: Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36
Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36 Open
View article: Spatial transcriptomics of murine bone marrow megakaryocytes at single-cell resolution
Spatial transcriptomics of murine bone marrow megakaryocytes at single-cell resolution Open
View article: Supp Table 6 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 6 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 6 qRT PCR Probes
View article: Supp Table 5 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 5 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 5 Antibodies
View article: Supp Table 1 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 1 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 1 VEGFAC Top Differentially Expressed Genes by Cluster
View article: Supp Table 1 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 1 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 1 VEGFAC Top Differentially Expressed Genes by Cluster
View article: Supp Table 7 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 7 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 7 NGS Panel
View article: Supplementary Information from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supplementary Information from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Materials and Methods, Supplementary Figures S1-S12
View article: Supp Table 3 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 3 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 3 HD and MPN samples.
View article: Supp Table 4 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 4 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
MM ALL Donor Details
View article: Data from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Data from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation pr…
View article: Supp Table 3 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supp Table 3 from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Table 3 HD and MPN samples.
View article: Supplementary Information from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Supplementary Information from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies Open
Supplementary Materials and Methods, Supplementary Figures S1-S12