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The December issue of Experimental Hematology is here!

Explore the latest findings, innovative studies and thought-provoking insights that continue to shape the field! Read the December Issue on ExpHem. 

Explore this Issue's Lineup:

Articles from the Special Issue on Chromatin Structure and Function

Three-dimensional genome reorganization in hematopoietic stem cells

Akihiro Nakajima, Keisuke Kirito, Mio Nakanishi, Naoya Takayama

Open Access

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Hematopoietic stem cells (HSCs) are defined by self-renewal, multipotency, stress response, metabolism, and quiescence. Advances in chromatin conformation capture reveal how the three-dimensional genome organization changes during development, activation, differentiation, and aging. This review covered chromatin remodeling, key transcription factors, epigenetic modifiers, and structural proteins in shaping HSC genome architecture, and how its disruption contributed to hematologic disorders, highlighting therapeutic prospects.

Brief Communications

Normal Hematopoiesis

Asrij/OCIAD1 expression delineates functionally distinct hematopoietic stem cells in the bone marrow

Aishwarya Prakash, Souvik Halder, Maneesha S. Inamdar

Open Access

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Using an Asrij-mNeonGreen fluorescent reporter mouse, our study addresses the complexities of hematopoietic stem cell (HSC) heterogeneity. We demonstrate that differential expression of the mitochondrial protein Asrij/OCIAD1 correlates with distinct HSC states. While low Asrij expression marks quiescent HSCs with robust self-renewal capacity, high Asrij expression identifies activated, differentiation-primed HSCs. Our findings identify Asrij as a novel regulator of HSC heterogeneity and introduce the Asrij-mNeonGreen reporter as a versatile tool for dissecting stem cell fate decisions in vivo.

Malignant Hematopoiesis

A 30-gene classifier distinguishes low-risk MDS HSPCs from healthy HSPCs

Pawan Bhat, Joseph C. Van Amburg, Chad R. Potts,...Robert S. Welner, Alexander G. Bick, Paul Brent Ferrell

Open Access

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We processed bone marrow-derived mononuclear cells (BMMCs) from 16 treatment-naïve LR-MDS patients for single-cell transcriptomics as previously described [5]. We integrated healthy donor (HD) single-cell libraries from eight age-matched donors from an external data set for comparison. The HD libraries underwent similar processing as our study cohort [6]. Patients provided written consent, and their samples were processed by the Vanderbilt Hematologic Tissue Repository at Vanderbilt University Medical Center.

Articles

New Techniques and Technologies

A xeno-free red blood cell differentiation formula models sickle cell disease from somatically sourced patient iPSCs

Ashlee J. Conway, Tolulope O. Rosanwo, Thomas E. Williamson,...Carlo Brugnara, Trista E. North, George Q. Daley

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Human derived induced pluripotent stem cells (iPSCs) offer multilineage potential, but modeling red blood cell (RBC) disorders such as sickle cell disease (SCD) is often hindered by immature erythrocytes lacking β-globin and poor enucleation. We presented an optimized three-stage, xeno-free protocol using polyvinyl alcohol to generate enucleated, β-globin+ RBCs from healthy and SCD donors. SCD iRBCs sickle under hypoxia, and RNA sequencing showed altered hemoglobin regulation and oxidative stress pathways. This method enables patient-specific iRBC production for in vitro SCD modeling and therapeutic development.

Malignant Hematopoiesis

An engineered IgM antibody targeting CD20 has enhanced complement-dependent cytotoxicity compared with an IgG

Kevin C. Hart, Paul R. Hinton, Marigold Manlusoc,... Maya F. Kotturi, Ramesh Baliga, Bruce A. Keyt

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Antibody-mediated complement-dependent cytotoxicity (CDC) involves the binding of monoclonal antibodies to target cells, followed by the recruitment and activation of the complement system, leading to cell lysis. For bivalent IgG antibodies, this process begins when antibodies recognize specific antigens on the surface of target cells, forming antibody-antigen complexes. The CDC activity of IgG antibodies is dependent on target antigen density [1,2]. Together, six IgG antibodies opsonize the target antigen and form a hexameric structure, which enables C1q to bind the antibody heavy chain Fc region and initiate the classical complement cell death pathway.

Nonmalignant hematological diseases

Mitochondrial retention and autophagy dysregulation drive oxidative stress in sickle cell disease erythrocytes

Jagadeesh Ramasamy, Prasanth Kumar Punathil Kannan, Sugasini Dhavamani, Savitha Palanimuthu, Robert Molokie, Angela Rivers

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Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the β-globin gene, producing hemoglobin-S (HbS). Under low oxygen conditions, HbS polymerizes, forming rigid structures that distort erythrocytes into a sickle shape, impairing their function and resulting in hemolysis. This deformation of erythrocytes reduces their lifespan from 90–120 days to 10–20 days. The consequences include impaired oxygen delivery, vascular occlusion, and tissue ischemia, which contribute to the hallmark symptoms of SCD, including chronic pain, anemia, and organ damage.