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Experimental Hematology has on average 25,000 articles download per month

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Expanded Potential Stem Cell Media as a tool to study human developmental hematopoiesis in vitroOpen in a New Window

The in vitro derivation and stabilization of pluripotent stem cells (PSCs) has afforded unprecedented insights into early mammalian development [1,2]. With the ability to form all embryonic germ layers, PSCs have been particularly important for studying human development where direct investigation of embryogenesis is severely constrained. Within hematology, in vitro PSC hematopoiesis has provided a powerful model to study early specification events in hematopoietic cell formation as well as the different waves of developmental hematopoiesis that occur during embryogenesis [3,4]; the primitive wave, transient definitive wave, and definitive wave [5,6].

 

Lineage marker expression on mouse hematopoietic stem cellsOpen in a New Window

Whether hematopoietic stem cells (HSCs) express lineage markers is controversial.In this study, we highly purified HSCs from the adult bone marrow of C57BL/6 mice and examined their gene expression and reconstitution potential. We first focused on the integrin family. Single-cell reverse transcription-polymerase chain reaction showed that the expression of ItgaM/Itgb2 (Mac-1) and Itga2b/Itgb3 (CD41/CD61) gradually increased along HSC differentiation while Itga4, Itga5, Itga6, and ItgaV (CD51) together with Itgb1 were highly expressed in both HSCs and hematopoietic progenitor cells (HPCs).

 

Transcription factor Oct1 protects against hematopoietic stress and promotes acute myeloid leukemiaOpen in a New Window

A better understanding of the development and progression of acute myelogenous leukemia (AML) is necessary in order to improve patient outcome. Here we define roles for the transcription factor Oct1/Pou2f1 in AML and normal hematopoiesis. Inappropriate re-activation of the Cdx2 gene is widely observed in leukemia patients and in leukemia mouse models. We show that Oct1 associates with the Cdx2 promoter in both normal and AML primary patient samples, but recruits the histone demethylase Jmjd1a/Kdm3a to remove the repressive H3K9me2 mark only in malignant specimens.

 

CD97 is associated with poor overall survival in Acute Myeloid LeukemiaOpen in a New Window

Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy characterized by clonal proliferation of myeloid precursors [1]. It is the most common acute leukemia in adults. Overall survival of patients with AML remains dismal (<50% for younger patients and <10% for older patients) due to the high rate of relapse [2]. Cytogenetic and molecular genetic alterations provide significant prognostic information for determining the response to chemotherapy and survival outcome.

 

Maintenance and enhancement of human PBSC engraftment after ex vivo culture via an HDACi/SALL4 axis (3465)Open in a New Window

Hematopoietic stem cells (HSCs) possess the unique capacity to self-renew and give rise to all types of mature cells within the blood and immune systems. HSC self-renewal is regulated by both intrinsic and extrinsic signals [1,2,3]. Genes and pathways that are functionally linked to self-renewal of HSCs include CEBPα [4], Notch ligands [5,6], Angiopoietin-like proteins [7], SALL4 [8], homeobox protein B4 (HOXB4) [9] and c-MPL [10]. Although self-renewal divisions of HSCs clearly occur in vivo, induction of such event ex vivo has been difficult.

 

Remission clone in acute myeloid leukemia shows growth advantage after chemotherapy but is distinct from leukemic cloneOpen in a New Window

Acute myeloid leukemia (AML) is a genetically and morphologically heterogenous disease [1,2]. In The Cancer Genome Atlas project, the average number of mutations per patient was 13, and 23 significant gene mutations were frequently found with a complex interplay of genetic mutations at diagnosis [3]. Many studies have investigated the functional roles of these mutations [4–7]. For example, DNMT3A-R882H is one of the most common mutations. Several studies have suggested that it likely arises in the preleukemic hematopoietic stem cell compartment; leads to inactivation of apoptosis, induction of stem cell expansion, and inhibition of differentiation; and has been shown to have reduced DNA methylation activity [5,6,8].

 

PSC-RED and MNC-RED: Albumin-free and low-transferrin robust erythroid differentiation protocols to produce human enucleated red blood cellsOpen in a New Window

Cultured red blood cells (cRBCs) are useful in studying erythroid disease mechanisms and hold great promise as reagent cells to diagnose allo-immunization and as a potential source of invaluable cells carrying rare blood groups that are necessary to transfuse allo-immunized patients [1,2]. Genetically modified cRBCs that express therapeutic proteins [1,3,4] are another highly promising avenue of research because relatively small numbers of such cells could be clinically useful, greatly decreasing the technical barriers to translation associated with transfusion applications [5].

 

Are transplantable stem cells required for adult hematopoiesis?Open in a New Window

Hematopoietic stem cells (HSCs) have been studied intensely for more than half a century. As a result, the properties of HSCs have become a paradigm of adult stem cell biology and function. The “classical” view of hematopoiesis suggests that the HSCs sit at the top of a hierarchy and that differentiation involves sequential production of multipotent and lineage committed progenitors with limited self-renewal capacity. This view of hematopoiesis is certainly valid after transplantation of HSCs, where, with appropriate support, a single HSC can regenerate the entire hematopoietic system of the recipient.

 

Fetal hemoglobin and F-cell variance in mobilized CD34+ cell-transplanted rhesus monkeysOpen in a New Window

Sickle cell disease (SCD) is a monogenic disorder caused by a missense mutation in the β-globin gene, which results in the production of sickle hemoglobin (HbS, α2βS2) that polymerizes under hypoxic conditions. Sickle erythrocytes occlude small blood vessels leading to ischemic tissue damage, resulting in severe pain and/or organ failure [1]. High fetal hemoglobin (HbF, α2γ2) levels are clinically beneficial for SCD patients as HbF inhibits deoxy HbS polymerization. Patients with hereditary persistence of fetal hemoglobin (HPFH) mutations and a typical evenly distributed 30% HbF expression are clinically asymptomatic despite having high HbS levels [2].

 

Translational regulation and deregulation in erythropoiesisOpen in a New Window

Protein synthesis is a well-orchestrated fundamental process that is tightly regulated in every organism. All cells share the basic machinery and mechanisms for translating mRNA into proteins; however, different cell types have specialized translational needs. Protein synthesis plays a key role in maintaining cellular homeostasis and is carefully regulated at both the transcription and translation levels. Although regulation of protein synthesis can occur at any one of the various stages of the translation pathway, it is translation initiation that is the key regulatory stage [1].

 

WITHDRAWN: Assessment of hematopoietic and neurologic pathophysiology of HCLS1-associated protein X-1 deficiency in a Hax1-knockout mouse modelOpen in a New Window

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

 

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7/25/2019
ISEH Summer Webinar: Changing views of lineage commitment

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