Using a novel Galc floxed allele, researchers induced ubiquitous galactosylceramidase ablation at various postnatal timepoints and identified a critical period of vulnerability to galactosylceramidase ablation between P4-6 in mice.
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Weinstock, N. I., Kreher, C., Favret, J., Nguyen, D., Bongarzone, E. R., Wrabetz, L., Laura Feltri, M., & Shin, D. (2020). Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease. Nature Communications, 11(1), 5356. https://doi.org/10.1038/s41467-020-19179-w Cite
To target acute myeloid leukemia blasts and leukemic stem cells using natural killer (NK) cells, scientists developed a trispecific killer engager molecule containing a humanized anti-CD16 heavy chain camelid single-domain antibody that activates NK cells.
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Arvindam, U. S., van Hauten, P. M. M., Schirm, D., Schaap, N., Hobo, W., Blazar, B. R., Vallera, D. A., Dolstra, H., Felices, M., & Miller, J. S. (2020). A trispecific killer engager molecule against CLEC12A effectively induces NK-cell mediated killing of AML cells. Leukemia, 1–11. https://doi.org/10.1038/s41375-020-01065-5 Cite
Researchers bring together what is currently known about chromatin status and the development of cells in the hematopoietic system under normal and abnormal conditions.
[Trends in Genetics]
Scientists examined the expression of ACE2, to which SARS-CoV-2 Spike protein binds to facilitate viral entry, in cord blood derived hematopoietic stem cells/hematopoietic progenitor cells and in peripheral blood derived immune cell subtypes.
[Stem Cell Reviews and Reports]
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Researchers showed that large invaginations were generated by microtubule constraints on the swelling nucleus of human hematopoietic stem and progenitor cells during early commitment toward the myeloid lineage.
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Biedzinski, S., Agsu, G., Vianay, B., Delord, M., Blanchoin, L., Larghero, J., Faivre, L., Théry, M., & Brunet, S. (2020). Microtubules control nuclear shape and gene expression during early stages of hematopoietic differentiation. The EMBO Journal, n/a(n/a), e103957. https://doi.org/10.15252/embj.2019103957 Cite
Researchers showed that mitochondrial membrane potential can be used to prospectively isolate chronologically old hematopoietic stem cells (HSCs) with transcriptional features and functional attributes characteristic of young HSCs, including a high rate of transcription and balanced lineage-affiliated programs.
[Cell Stem Cell]
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Through single-cell RNA sequencing, researchers identified the expression of Dach1 and associated genes in this fraction as being coexpressed with myeloid/stem genes but inversely correlated with lymphoid genes.
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Amann-Zalcenstein, D., Tian, L., Schreuder, J., Tomei, S., Lin, D. S., Fairfax, K. A., Bolden, J. E., McKenzie, M. D., Jarratt, A., Hilton, A., Jackson, J. T., Di Rago, L., McCormack, M. P., de Graaf, C. A., Stonehouse, O., Taoudi, S., Alexander, W. S., Nutt, S. L., Ritchie, M. E., … Naik, S. H. (2020). A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics. Nature Immunology, 1–11. https://doi.org/10.1038/s41590-020-0799-x Cite
Scientists review evidence of signals emerging from hematopoietic stem and progenitor cells through secreted autocrine or paracrine factors, including extracellular vesicles, and via direct contact within the niche.
Researchers describe an optimized laboratory-scale workflow whereby lentiviral vector (LV)-containing supernatant was purified and concentrated by sequential chromatographic steps, obtaining biologically active LVs with infectious titer and specific activity in the order of 109 Transducing Unit (TU)/ml and 5×104 TU/ng of HIV Gag p24, respectively.
[Molecular Therapy-Methods & Clinical Development]
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Soldi, M., Sergi, L. S., Unali, G., Kerzel, T., Cuccovillo, I., Capasso, P., Annoni, A., Biffi, M., Rancoita, P. M. V., Cantore, A., Lombardo, A., Naldini, L., Squadrito, M. L., & Kajaste-Rudnitski, A. (2020). Laboratory-scale lentiviral vector production and purification for enhanced ex vivo and in vivo genetic engineering. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2020.10.009 Cite
Inadequate hematopoietic stem cell infusion dose did not negatively impact autologous hematopoietic stem cell transplantation patient survival but significantly prolonged the time to hematopoietic engraftment.
[Leukemia & Lymphoma]
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Liu, W., Wu, M., Xie, Y., Zhang, C., Ping, L., Feng, F., Leng, X., Mi, L., Wang, X., Zhu, J., & Song, Y. (2020). Autologous hematopoietic stem cell transplantation with inadequate stem cell dose in patients with non-Hodgkin lymphoma. Leukemia & Lymphoma, 0(0), 1–7. https://doi.org/10.1080/10428194.2020.1834092 Cite
The authors investigated the pro-hematopoietic effects and underlying mechanisms of ziyuglycoside II in cyclophosphamide-induced leukopenia in mice.
[Biomedicine & Pharmacotherapy]
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Fang, H., Xie, X., Liu, P., Rao, Y., Cui, Y., Yang, S., Yu, J., Luo, Y., & Feng, Y. (2020). Ziyuglycoside II alleviates cyclophosphamide-induced leukopenia in mice via regulation of HSPC proliferation and differentiation. Biomedicine & Pharmacotherapy, 132, 110862. https://doi.org/10.1016/j.biopha.2020.110862 Cite