Transplantation of hematopoietic stem cells (HSCs) from human umbilical cord blood (hUCB) holds great promise for treating a broad spectrum of hematological disorders including cancer. However, the limited number of HSCs in a single hUCB unit restricts its widespread use. Although extensive efforts have led to multiple methods for ex vivo expansion of human HSCs by targeting single molecules or pathways, it remains unknown whether it is possible to simultaneously manipulate the large number of targets essential for stem cell self-renewal. Recent studies indicate that N-methyladenosine (mA) modulates the expression of a group of mRNAs critical for stem cell-fate determination by influencing their stability. Among several mA readers, YTHDF2 is recognized as promoting targeted mRNA decay. However, the physiological functions of YTHDF2 in adult stem cells are unknown. Here we show that following the conditional knockout (KO) of mouse Ythdf2 the numbers of functional HSC were increased without skewing lineage differentiation or leading to hematopoietic malignancies. Furthermore, knockdown (KD) of human YTHDF2 led to more than a 10-fold increase in the ex vivo expansion of hUCB HSCs, a fivefold increase in colony-forming units (CFUs), and more than an eightfold increase in functional hUCB HSCs in the secondary serial of a limiting dilution transplantation assay. Mapping of mA in RNAs from mouse hematopoietic stem and progenitor cells (HSPCs) as well as from hUCB HSCs revealed its enrichment in mRNAs encoding transcription factors critical for stem cell self-renewal. These mA-marked mRNAs were recognized by Ythdf2 and underwent decay. In Ythdf2 KO HSPCs and YTHDF2 KD hUCB HSCs, these mRNAs were stabilized, facilitating HSC expansion. Knocking down one of YTHDF2's key targets, Tal1 mRNA, partially rescued the phenotype. Our study provides the first demonstration of the function of YTHDF2 in adult stem cell maintenance and identifies its important role in regulating HSC ex vivo expansion by regulating the stability of multiple mRNAs critical for HSC self-renewal, thus identifying potential for future clinical applications.

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SUMMARY Regulation of hematopoietic stem cells (HSCs) by bone marrow (BM) niches has been extensively studied; however, whether and how HSC subpopulations are distinctively regulated by BM niches remain unclear. Here, we functionally distinguished reserve HSCs (rHSCs) from primed HSCs (pHSCs) based on their response to chemotherapy and examined how they are dichotomously regulated by BM niches. Both pHSCs and rHSCs supported long-term hematopoiesis in homeostasis; however, pHSCs were sensitive but rHSCs were resistant to chemotherapy. Surviving rHSCs restored the HSC pool and supported hematopoietic regeneration after chemotherapy. The rHSCs were preferentially maintained in the endosteal region that enriches N-cadherin+ (N-cad+) bone-lining cells in homeostasis and post-chemotherapy. N-cad+ cells were functional bone and marrow stromal progenitor cells (BMSPCs), giving rise to osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Finally, ablation of N-cad+ niche cells or deletion of SCF from N-cad+ niche cells impaired rHSC maintenance during homeostasis and regeneration.

Pd/CeO 2 has attracted great attention owing to its unique activity for methane catalytic oxidation; however, the active sites for CH 4 catalytic oxidation still remain elusive, which affects the comprehensive understanding of the catalytic mechanism. In this work, the structures of PdO x nanoparticles (NPs) loaded on octahedrons, cubes, and rods of nanocrystal CeO 2 supports were systematically studied by Cs-corrected HRTEM/STEM, XPS, and Raman spectroscopy. Our results indicate that the Pd species on CeO 2 supports are morphology-dependent: PdO NPs (Pd 2+ ) on octahedrons, PdO x (x = 1−2) clusters (1−2 nm) on cubes, and dispersed Pd 4+ ions on the CeO 2 rods. Additionally, the chemical states of Pd can be tuned in oxidizing/reducing atmospheres via interactions between Pd and CeO 2 . Detailed studies reveal that the Pd 2+ species are the active centers for the catalytic oxidation of methane. The activity of Pd 0 could be ascribed to Pd 2+ produced through the gradual oxidation of Pd 0 during the CH 4 oxidation. Further, Pd 4+ in the CeO 2 lattice is inactive for CH 4 oxidation. In situ Fourier transform infrared spectroscopy results suggest that the mechanism of CH 4 oxidation reaction on PdO x /CeO 2 follows the Mars−van Krevelen mechanism, and adsorbed CO can be produced in CH 4 decomposition over Pd 2+ in the absence of gas-phase oxygen. As revealed by density functional theory calculations, the incomplete coordination of Pd 2+ ions and adjacent oxygen atoms has excellent activity in cracking the C−H bond of CH 4 , which leads to high methane oxidation ability.

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The strong metal-support interaction (SMSI) is widely used in supported metal catalysts and extensive studies have been performed to understand it. Although considerable progress has been achieved, the surface structure of the support, as an important influencing factor,isusually ignored. We report af acet-dependent SMSI of Pd-TiO 2 in oxygen by using in situ atmospheric pressure TEM. Pd NPs supported on TiO 2 ( 101) and (100) surfaces showed encapsulation. In contrast, no such cover layer was observed in Pd-TiO 2 (001) catalyst under the same conditions.This facet-dependent SMSI, which originates from the variable surface structure of the support, was demonstrated in ap robe reaction of methane combustion catalyzedb yP d-TiO 2 .O ur discovery of the oxidative facet-dependent SMSI gives direct evidence of the important role of the support surface structure in SMSI and provides anew way to tune the interaction between metal NPs and the support as well as catalytic activity.

Soybean Knowledge Base (http://soykb.org) is a comprehensive web resource developed for bridging soybean translational genomics and molecular breeding research. It provides information for six entities including genes/proteins, microRNAs/sRNAs, metabolites, single nucleotide polymorphisms, plant introduction lines and traits. It also incorporates many multi-omics datasets including transcriptomics, proteomics, metabolomics and molecular breeding data, such as quantitative trait loci, traits and germplasm information. Soybean Knowledge Base has a new suite of tools such as In Silico Breeding Program for soybean breeding, which includes a graphical chromosome visualizer for ease of navigation. It integrates quantitative trait loci, traits and germplasm information along with genomic variation data, such as single nucleotide polymorphisms, insertions, deletions and genome-wide association studies data, from multiple soybean cultivars and Glycine soja.