Desmond Wai Loon Chin
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View article: An Upstream <scp> <i>RUNX3</i> </scp> Enhancer, <scp>eR3</scp> (−18m/−28h), Regulates the Development of Gut‐Associated Anti‐Tumorigenic <scp>CD8</scp> <sup>+</sup> <scp>CD103</scp> <sup>+</sup> Cytotoxic T Lymphocytes in Mouse and Human
An Upstream <span> <i>RUNX3</i> </span> Enhancer, <span>eR3</span> (−18m/−28h), Regulates the Development of Gut‐Associated Anti‐Tumorigenic <span>CD8</span> <sup>+</sup> <span>CD103</span> <sup>+</sup> Cytotoxic T Lymphocytes in Mouse and Human Open
The RUNX3 gene is frequently involved in a variety of cancers and immunological diseases. Despite such widespread association with human diseases, the transcriptional regulation of RUNX3 remains elusive. Here we report the identification o…
View article: Decitabine‐Driven Foetal Haemoglobin Induction in Townes Mice and Human Erythroblasts
Decitabine‐Driven Foetal Haemoglobin Induction in Townes Mice and Human Erythroblasts Open
Background Induction of foetal haemoglobin (HbF) is a clinically validated approach to modulate the severity of sickle cell disease (SCD). This manuscript evaluates the efficacy of decitabine, a DNA methyltransferase (DNMT) inhibitor, in i…
View article: Murine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine
Murine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine Open
X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are uncommon diseases caused by loss-of-function and gain-of-function mutations, respectively, in the erythroid form of 5-aminolevulinic acid synthetase (ALAS), ALAS2,…
View article: Phospholipid metabolic adaptation promotes survival of <i>IDH2</i> mutant acute myeloid leukemia cells
Phospholipid metabolic adaptation promotes survival of <i>IDH2</i> mutant acute myeloid leukemia cells Open
Genetic mutations in the isocitrate dehydrogenase ( IDH ) gene that result in a pathological enzymatic activity to produce oncometabolite have been detected in acute myeloid leukemia (AML) patients. While specific inhibitors that target mu…
View article: Panhematopoietic RNA barcoding enables kinetic measurements of nucleate and anucleate lineages and the activation of myeloid clones following acute platelet depletion
Panhematopoietic RNA barcoding enables kinetic measurements of nucleate and anucleate lineages and the activation of myeloid clones following acute platelet depletion Open
Background Platelets and erythrocytes constitute over 95% of all hematopoietic stem cell output. However, the clonal dynamics of HSC contribution to these lineages remains largely unexplored. Results We use lentiviral genetic labeling of m…
View article: Aged healthy mice acquire clonal hematopoiesis mutations
Aged healthy mice acquire clonal hematopoiesis mutations Open
Chin and colleagues used detailed mutational analysis of aged mice and transplantation to evaluate the mouse as a model of clonal hematopoiesis (CH). Their data suggest that while murine hematopoietic stem cells acquire mutations in CH-ass…
View article: Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation
Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation Open
Hematopoietic stem cells (HSC) rarely divide, rest in quiescence, and proliferate only upon stress hematopoiesis. The cytokine thrombopoietin (Thpo) has been perplexingly described to induce quiescence and promote self-renewal divisions in…
View article: Thrombopoietin maintains cell numbers of hematopoietic stem and progenitor cells with megakaryopoietic potential
Thrombopoietin maintains cell numbers of hematopoietic stem and progenitor cells with megakaryopoietic potential Open
Thrombopoietin (THPO) has long been known to influence megakaryopoiesis and hematopoietic stem and progenitor cells (HSPCs), though the exact mechanisms through which it acts are unknown. Here we show that MPL expression correlates with me…
View article: High mitochondrial mass is associated with reconstitution capacity and quiescence of hematopoietic stem cells
High mitochondrial mass is associated with reconstitution capacity and quiescence of hematopoietic stem cells Open
Key Points HSCs can be separated based on high or low mitochondrial mass. Higher mitochondrial mass is associated with quiescence and greater reconstitution capacity of HSCs.
View article: Abstract 971: PRMT5 modulates splicing for genome integrity and preserves proteostasis of hematopoietic stem cells
Abstract 971: PRMT5 modulates splicing for genome integrity and preserves proteostasis of hematopoietic stem cells Open
Protein arginine methyltransferase 5 (PRMT5) has recently been identified as a promising therapeutic target in various solid and hematologic cancers, while PRMT5 inhibitors are currently in clinical development. Functionally, PRMT5 has an …
View article: PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells
PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells Open
Protein arginine methyltransferase 5 (PRMT5) is essential for hematopoiesis, while PRMT5 inhibition remains a promising therapeutic strategy against various cancers. Here, we demonstrate that hematopoietic stem cell (HSC) quiescence and vi…
View article: Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis
Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis Open
Key Points Canonical Notch signaling is dispensable for steady-state and posttransplantation myelopoiesis, as well as stress erythropoiesis. Key lineage regulators and Notch target genes are expressed independent of canonical Notch signali…