Coinhibition of Activated p38 MAPKα and mTORC1 Potentiates Stemness Maintenance of HSCs from SR1 -Expanded Human Cord Blood CD34+ Cells via Inhibition of Senescence

Investigators showed that cellular senescence occurred in the Stem Regenin 1‐expanded hUCB CD34+ cells in which p38 mitogen‐activated protein kinase α (p38α) and mammalian target of rapamycin complex 1 (mTORC1) were successively activated.
[Stem Cells Translational Medicine]
Li, X., Ma, X., Chen, Y., Peng, D., Wang, H., Chen, S., … Liu, L. (n.d.). Coinhibition of activated p38 MAPKα and mTORC1 potentiates stemness maintenance of HSCs from SR1-expanded human cord blood CD34+ cells via inhibition of senescence. STEM CELLS Translational Medicine, n/a(n/a). https://doi.org/10.1002/sctm.20-0129 Cite
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Engineering Monocyte/Macrophage−Specific Glucocerebrosidase Expression in Human Hematopoietic Stem Cells Using Genome Editing

Researchers report an efficient CRISPR/Cas9-based approach that targets glucocerebrosidase expression cassettes with a monocyte/macrophage-specific element to the CCR5 safe-harbor locus in human hematopoietic stem and progenitor cells.
[Nature Communications]
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Single Cell Analyses and Machine Learning Define Hematopoietic Progenitor and HSC-Like Cells Derived from Human PSCs

To define the dynamics and heterogeneity of hematopoietic stem and progenitor cells (HSPCs) that can be generated in vitro from human pluripotent stem cells, scientists exploited single cell RNA sequencing in combination with single cell protein expression analysis.
[Blood]
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Hematopoietic Stem Cells Acquire Survival Advantage by Loss of RUNX1 Methylation Identified in Familial Leukemia

The authors performed targeted deep sequencing on a family with three occurrences of acute myeloid leukemia and identified a novel RUNX1 mutation R237K.
[Blood]
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Driver Mutations in Leukemia Promote Disease Pathogenesis through a Combination of Cell-Autonomous and Niche Modulation

Researchers showed that constitutive and early loss of the epigenetic regulator, TET2, when combined with constitutive activation of FLT3, results in transformation of chronic myelomonocytic leukemia-like or myeloproliferative neoplasm-like phenotype to acute myeloid leukemia, which is more pronounced in double-mutant mice relative to mice carrying mutations in single genes.
[Stem Cell Reports]
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HSPG2 Overexpression Independently Predicts Poor Survival in Patients with Acute Myeloid Leukemia

The mRNA expression level of heparan sulfate proteoglycan 2 (HSPG2) in bone marrow mononuclear cells and CD34+ hematopoietic stem/progenitor cells obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR.
[Cell Death & Disease]
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The BET Inhibitor CPI203 Promotes Ex Vivo Expansion of Cord Blood Long-Term Repopulating HSCs and Megakaryocytes

Of 10 compounds tested, only the Bromodomain and Extra-terminal Motif inhibitor CPI203 enhanced the expansion of human cord blood hematopoietic stem cells without losing cell viability in vitro.
[Blood]
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Activation of the Receptor Tyrosine Kinase, RET, Improves Long-Term Hematopoietic Stem Cell Outgrowth and Potency

Researchers demonstrated a role for the glial family ligand receptor, RET, at the cell surface of hematopoietic stem cells, in mediating sustained cellular growth, resistance to stress and improved cell survival throughout in vitro expansion.
[Blood]
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The Source and Dynamics of Adult Hematopoiesis: Insights from Lineage Tracing

The authors review recent advances in the understanding of native hematopoiesis, focusing in particular on the application of genetic lineage tracing in mice.
[Annual Review of Cell and Developmental Biology]
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Co‑Transplantation of Tonsil‑Derived Mesenchymal Stromal Cells in Bone Marrow Transplantation Promotes Thymus Regeneration and T Cell Diversity following Cytotoxic Conditioning

Researchers found that the co‑transplantation of tonsil‑derived mesenchymal stromal cells (T‑MSCs) with bone marrow‑derived cells (BMCs) accelerated the recovery of involuted thymuses in mice following partial pre‑bone marrow transplantation conditioning with busulfan‑cyclophosphamide treatment, possibly by inducing FMS‑like tyrosine kinase 3 ligand and fibroblast growth factor 7 production in T‑MSCs.
[International Journal of Molecular Medicine]
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Efficient Gene Editing of Human Long-Term Hematopoietic Stem Cells Validated by Clonal Tracking

Investigators applied a barcoding strategy to clonal tracking of edited cells and showed that editing activated p53, which substantially shrank the hematopoietic stem cell clonal repertoire in hematochimeric mice, although engrafted edited clones preserved multilineage and self-renewing capacity.
[Nature Biotechnology]
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