Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage

神経幹細胞の運命を決める分子を発見 --脳形成機構の解明と脳腫瘍や精神疾患の治療法に期待--. 京都大学プレスリリース. 2020-09-28.During brain development, neural stem cells (NSCs) initially produce neurons and change their fate to generate glias. While the regulation of neurogenesis is well characterized, specific markers for glial precursor cells (GPCs) and the master regulators for gliogenesis remain unidentified. Accumulating evidence suggests that RNA-binding proteins (RBPs) have significant roles in neuronal development and function, as they comprehensively regulate the expression of target genes in a cell-type-specific manner. We systematically investigated the expression profiles of 1, 436 murine RBPs in the developing mouse brain and identified quaking (Qk) as a marker of the putative GPC population. Functional analysis of the NSC-specific Qk-null mutant mouse revealed the key role of Qk in astrocyte and oligodendrocyte generation and differentiation from NSCs. Mechanistically, Qk upregulates gliogenic genes via quaking response elements in their 3′ untranslated regions. These results provide crucial directions for identifying GPCs and deciphering the regulatory mechanisms of gliogenesis from NSCs

Determination of trace elements in natural water samples by air-segmented flow-injection/ICP-MS after preconcentration with a chitosan-based chelating resin

本法では,各種天然水中の極微量金属成分を同時定量する目的で空気分節試料導入/ICP-MSシステムを用いて,微少量試料(数十μl)を前処理せずにネブライザーに送り込み,多数の金属成分の定量が可能であった。共存主成分による質量干渉を受ける一部遷移金属や直接試料導入では感度の足りない元素については,イミノ二酢酸型キトサンキレート樹脂充填カラムによる分離·濃縮操作の併用によって更に信頼性の高いデータが得られることが分かった。前処理においては,体積1mlのミニカラムを用いて50mlの溶液試料から50倍濃縮を行い,試料·試薬·廃液すべてを少量化することができた。本ICP-MSシステムでは試料導入量は80μlで十分であり,1mlでも数回繰り返し測定が可能で,しかも多元素同時分析ができた。確立した分析法を用いて河川水や市販のミネラルウォーターに応用し,希土類を含め45種の微量元素の定量が可能となった。Ultratrace elements in natural water samples were determined simultaneously by air-segmented flow-injection/inductively coupled plasma-mass spectrometry(SFI/ICP-MS).A small volume of the sample solutions(80μl) was introduced into a nebulizer by an air-segmented flow-injection(SFI) system, and a maximum of fifteen elements were measured during each run.A chitosan-based chelating resin containing functional groups of iminodiacetate was used to separate and enrich analyte metal ions.A 50-fold preconcentration using 50ml of sample solutions was achieved by the proposed method, where 1ml of 0.1M nitric acid was added to residues after drying the chelating column effluent.At pH6, several heavy metals(Fe, Ni, Co, Cu, Zn, Ag, Cd, Pb and U) and rare earth elements(REEs) were quantitatively retained on the chelating resin column, whereas alkali and alkaline earth metals were eluted from the column by rinsing with 5ml of a 0.2M ammonium acetate solution.Metals adsorbed on the chelating resin column were recovered by elution with 10ml of 1M nitric acid.The proposed method was applied to the determination of trace elements in several natural water samples, such as river water and mineral drinking water

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target