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Timmons Lowry posted an update 6 months, 3 weeks ago
Malignant stem cells have long been considered a key therapeutic target in leukemia. Therapeutic strategies designed to target the fundamental biology of leukemia stem cells while sparing normal hematopoietic cells may provide better outcomes for leukemia patients. One process in leukemia stem cell biology that has intriguing therapeutic potential is energy metabolism. In this article we discuss the metabolic properties of leukemia stem cells and how targeting energy metabolism may provide more effective therapeutic regimens for leukemia patients. In addition, we highlight the similarities and differences in energy metabolism between leukemia stem cells and malignant stem cells from solid tumors.The depth of quiescence in hematopoietic stem cells (HSCs) dictates their potency and is sensitive to metabolic perturbations. Recent evidence suggests that lysosomal functions distinct from autophagic processes are pivotal in regulating quiescence versus activation by potential control of the access to a nutrient reservoir required for HSC activation.In this forum piece, we review progress in exploiting diet and nutrition for enhancing tissue regeneration with a particular emphasis on how dietary composition and diet-induced physiology influence adult stem cell biology.COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.In this issue of Cell Stem Cell, Ning et al. (2021) demonstrate that contractility in differentiating, suprabasally located keratinocytes acts non-cell-autonomously to regulate the replication and differentiation of the stem/progenitor keratinocytes in the basal layer of epidermis. This finding expands our understanding of the niche that regulates stem/progenitor cells in skin.By single-cell transcriptome profiling of human yolk sacs and fetal livers, Wang et al. (2021) (in this issue of Cell Stem Cell) track two alternative routes for differentiation of megakaryocytes. The authors have shown that these megakaryocytes have hemostatic- and HSC-supporting functions, and that hESC-derived thrombospondin1-positive endothelial cells are capable of generating megakaryocytes in vitro.Previous work demonstrating the existence of intermediate pluripotency states in post-implantation embryos had ignited a debate on whether “formative” pluripotency can be stabilized in pluripotent stem cell (PSC) lines. In this issue of Cell Stem Cell, two papers show that polarized epithelial and germ cell-competent formative PSCs can be maintained in modified activin-dependent conditions.Myeloproliferative neoplasms (MPNs) are hematological malignancies caused by somatic mutations originating from a single hematopoietic stem cell (HSC). In this issue of Cell Stem Cell,Van Egeren et al. (2021) used whole-genome sequencing of hematopoietic colonies to reconstruct the clonal history and time of acquisition of the disease-initiating gene mutation.This article shows an example of the peer review process for “Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis” (Ranzoni et al., 2021).Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.Divergence of gene function is a hallmark of evolution, but assessing functional divergence over deep time is not trivial. The few alleles available for cross-species studies often fail to expose the entire functional spectrum of genes, potentially obscuring deeply conserved pleiotropic roles. Here, we explore the functional divergence of WUSCHEL HOMEOBOX9 (WOX9), suggested to have species-specific roles in embryo and inflorescence development. Using a cis-regulatory editing drive system, we generate a comprehensive allelic series in tomato, which revealed hidden pleiotropic roles for WOX9. Analysis of accessible chromatin and conserved cis-regulatory sequences identifies the regions responsible for this pleiotropic activity, the functions of which are conserved in groundcherry, a tomato relative. Mimicking these alleles in Arabidopsis, distantly related to tomato and groundcherry, reveals new inflorescence phenotypes, exposing a deeply conserved pleiotropy. We suggest that targeted cis-regulatory mutations can uncover conserved gene functions and reduce undesirable effects in crop improvement.
Extensive resection of skin carcinomas in the periorbital and forehead regions often results in complicated defects involving the upper eyelid, superciliary arch, and nasal dorsum. The aim of this study is to report our experience with the use of supraorbital artery perforator propeller flaps for primary repair of complicated forehead defects.
A total of 6 patients underwent carcinoma resection with primary surgical reconstruction using supraorbital propeller flap at the Peking University School and Hospital of Stomatology from December 2015 to December 2018. We describe the technique and retrospectively review the outcomes.
A single propeller flap was used in 5 patients and 2 propeller flaps (supraorbital and nasolabial artery propeller flaps) in 1 patient. Hexa-D-arginine concentration Two patients developed venous congestion of the flap on the first postoperative day; however, in both cases it was relieved by multiple needle punctures. All flaps had survived well at 1-year follow-up. Five patients had a normal eyelid closure, but 1 patient presented with lagophthalmos, which required correction by secondary surgery.