Aging of Human Hematopoietic Stem Cells Is Linked to Changes in Cdc42 Activity

Investigators report increased frequencies of hematopoietic stem cell (HSC), HPC and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSCs further exhibited a delay in initiating division ex vivo though without changes in their division kinetics.
[Haematologica]
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Oncogenic N-Ras Mitigates Oxidative Stress-Induced Apoptosis of Hematopoietic Stem Cells

The authors expressed oncogenic NrasG12D within the hematopoietic system in mice and interrogated its effects on hematopoietic stem cell survival.
[Cancer Research]
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Circulating Tumor DNA Is Detectable in Canine Histiocytic Sarcoma, Oral Malignant Melanoma, and Multicentric Lymphoma

Researchers used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. They detected circulating tumor DNA in 21/23 of histiocytic sarcoma, 2/8of oral melanoma, and 12/13 of lymphoma cases.
[Scientific Reports]
Prouteau, A., Denis, J. A., De Fornel, P., Cadieu, E., Derrien, T., Kergal, C., Botherel, N., Ulvé, R., Rault, M., Bouzidi, A., François, R., Dorso, L., Lespagnol, A., Devauchelle, P., Abadie, J., André, C., & Hédan, B. (2021). Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma. Scientific Reports, 11(1), 877. https://doi.org/10.1038/s41598-020-80332-y Cite
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Developmental Stage-Specific Changes in Protein Synthesis Differentially Sensitize Hematopoietic Stem Cells and Erythroid Progenitors to Impaired Ribosome Biogenesis

Investigators showed that protein synthesis rates declined during hematopoietic stem cell (HSC) ontogeny, yet erythroid protein synthesis rates increased. A ribosomal mutation that impairs ribosome biogenesis disrupted both fetal and adult HSC self-renewal.
[Stem Cell Reports]
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Non-Viral Ex Vivo Genome-Editing in Mouse Bona Fide Hematopoietic Stem Cells with CRISPR/Cas9

The authors conducted two lines of genome-editing experiments of mouse hematopoietic stem cells (HSCs) with the clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein 9 (Cas9).
[Molecular Therapy-Methods & Clinical Development]
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The T-Box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors

Investigators demonstrated using an embryonic stem cell model that transient expression of the T-box transcription factor Eomesodermin governed hemogenic competency of extra-embryonic mesoderm.
[Nature Cell Biology]
Harland, L. T. G., Simon, C. S., Senft, A. D., Costello, I., Greder, L., Imaz-Rosshandler, I., Göttgens, B., Marioni, J. C., Bikoff, E. K., Porcher, C., de Bruijn, M. F. T. R., & Robertson, E. J. (2021). The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors. Nature Cell Biology, 23(1), 61–74. https://doi.org/10.1038/s41556-020-00611-8 Cite
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Development of Hematopoietic Syndrome Mice Model for Localized Radiation Exposure

Researchers developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure.
[Scientific Reports]
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Identification of miR-320 Family Members as Potential Diagnostic and Prognostic Biomarkers in Myelodysplastic Syndromes

Scientists identified novel potential microRNAs bound up with the diagnosis and prognosis of myelodysplastic syndromes (MDS). miRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients.
[Scientific Reports]
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Zfp521 Is Essential for the Quiescence and Maintenance of Adult Hematopoietic Stem Cells under Stress

Scientists found that Zinc finger protein 521 (Zfp521) deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, Zfp521-null chimeric mice showed significantly reduced pool size of hematopoietic stem cells and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence.
[iScience]
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UM171 Preserves Epigenetic Marks that Are Reduced in Ex Vivo Culture of Human HSCs via Potentiation of the CLR3-KBTBD4 Complex

Scientists report that UM171 potentiated the activity of a CULLIN3-E3 ubiquitin ligase complex whose target specificity was dictated by the poorly characterized Kelch/BTB domain protein KBTBD4.
[Cell Stem Cell]
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Targeting Leukemia-Initiating Cells in Acute Lymphoblastic Leukemia (ALL)

The authors review several biological and clinical aspects related to leukemia-initiating cells (LICs) in acute lymphoblastic leukemia (ALL), including: 1) immunophenotypic characterization of LIC-enriched subsets in human and mouse models of ALL; 2) emerging therapeutics against regulatory signaling pathways involved in LIC progression and maintenance in T- and B-cell leukemias; 3) novel epigenetic and age-related mechanisms of LIC propagation, and 4) ongoing efforts in immunotherapy to eradicate LIC-enriched cell subsets in relapsed and refractory ALL cases.
[Cancer Research]
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