A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia.

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases.

The genomic basis of childhood T-lineage acute lymphoblastic leukaemia.

T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes.

Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes.

Identification and targeting of treatment resistant progenitor populations in T-cell Acute Lymphoblastic Leukemia.

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to cure in T-cell Acute Lymphoblastic Leukemia (T-ALL). Biomarker guided risk stratification and targeted therapy have the potential to improve outcomes in high-risk T-ALL; however, cellular and genetic factors contributing to treatment resistance remain unknown. Previous bulk genomic studies in T-ALL have implicated tumor heterogeneity as an unexplored mechanism for treatment failure.

Decade-long leukaemia remissions with persistence of CD4 CAR T cells.

The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia who achieved a complete remission in 2010.

Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy.

The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients.

Diverse molecular compositions of dissolved organic matter derived from different composts using ESI FT-ICR MS.

Dissolved organic matter (DOM) derived from various composts can promote significant changes of soil properties. However, little is known about the DOM compositions and their similarities and differences at the molecular level. In this study, the molecular compositions of DOM derived from kitchen waste compost (KWC), green waste compost (GWC), manure waste compost (MWC), and sewage sludge compost (SSC) were characterized by electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS).

Diverse noncoding mutations contribute to deregulation of cis-regulatory landscape in pediatric cancers.

Interpreting the function of noncoding mutations in cancer genomes remains a major challenge. Here, we developed a computational framework to identify putative causal noncoding mutations of all classes by joint analysis of mutation and gene expression data. We identified thousands of SNVs/small indels and structural variants as putative causal mutations in five major pediatric cancers.

Transcriptional regulatory network controlling the ontogeny of hematopoietic stem cells.

Hematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-seq and histone mark ChIP-seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in mice. The five populations analyzed were embryonic day 10.

Developmental trajectory of prehematopoietic stem cell formation from endothelium.

Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the major arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters (IAC) before colonizing the fetal liver. To examine the cell and molecular transitions between endothelial (E), HE, and IAC cells, and the heterogeneity of HSPCs within IACs, we profiled ∼40 000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of 9.

scATAC-pro: a comprehensive workbench for single-cell chromatin accessibility sequencing data.

Single-cell chromatin accessibility sequencing has become a powerful technology for understanding epigenetic heterogeneity of complex tissues. However, there is a lack of open-source software for comprehensive processing, analysis, and visualization of such data generated using all existing experimental protocols. Here, we present scATAC-pro for quality assessment, analysis, and visualization of single-cell chromatin accessibility sequencing data.

SciBet as a portable and fast single cell type identifier.

Fast, robust and technology-independent computational methods are needed for supervised cell type annotation of single-cell RNA sequencing data. We present SciBet, a supervised cell type identifier that accurately predicts cell identity for newly sequenced cells with order-of-magnitude speed advantage. We enable web client deployment of SciBet for rapid local computation without uploading local data to the server.

Analytical dataset on the molecular compositional changes of dissolved organic matter during hyperthermophilic composting.

The aim of this research work was to determine the molecular compositional changes of dissolved organic matter (DOM) taken from different phases of the hyperthermophilic composting (HTC) process. The DOM samples were extracted by the standard protocol of C18 extraction methodology, and then analyzed by electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). The profiles of negative ion mass spectrum and DOM molecular formulas of four compost samples were reported.

Molecular insights into the transformation of dissolved organic matter during hyperthermophilic composting using ESI FT-ICR MS.

The aim of this work was to study the molecular compositional changes of dissolved organic matter (DOM) during hyperthermophilic composting (HTC) using electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. Our results reveal that DOM in hyperthermophilic compost mainly consisted of lignins/carboxylic-rich alicyclic molecules (72%) with relatively lower H/C (1.24), and the higher double bound equivalent (5.

A dual-signal output ratiometric electrochemiluminescent sensor for NADH detection.

Ratiometric electrochemiluminescence (ECL) has attracted great attention in the field of electrochemical analysis. In this study, a dual-signal-output ratiometric ECL sensor was developed for the detection of nicotinamide adenine dinucleotide (NADH). Nitrogen-doped graphene quantum dots (NGQDs) exhibit double ECL signal output capability, without the requirement of additional coreactants.

Ternary Z-scheme heterojunction of BiWO with reduced graphene oxide (rGO) and meso-tetra (4-carboxyphenyl) porphyrin (TCPP) for enhanced visible-light photocatalysis.

A highly efficient and new ternary TCPP/rGO/BiWO Z-scheme heterojunction was designed and fabricated via a facile hydrothermal approach and a liquid ultrasonic route in sequence. The crystal structures, morphologies, microstructures, chemical compositions, elemental states, optical and photo-electrochemical properties of the heterojunction were characterized. This Z-scheme TCPP/rGO/BiWO photocatalyst has significantly enhanced photocatalytic activity for the tetracycline (TC) degradation under the irradiation of visible light (λ > 420 nm) within 60 min, as compared to pure BiWO, rGO/BiWO and TCPP/BiWO composites.

RUNX1 and the endothelial origin of blood.

The transcription factor RUNX1 is required in the embryo for formation of the adult hematopoietic system. Here, we describe the seminal findings that led to the discovery of RUNX1 and of its critical role in blood cell formation in the embryo from hemogenic endothelium (HE). We also present RNA-sequencing data demonstrating that HE cells in different anatomic sites, which produce hematopoietic progenitors with dissimilar differentiation potentials, are molecularly distinct.

CD8 T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections.

Differentiation of effector and memory CD8 T cells is accompanied by extensive changes in the transcriptome and histone modifications at gene promoters; however, the enhancer repertoire and associated gene regulatory networks are poorly defined. Using histone mark chromatin immunoprecipitation coupled with deep sequencing, we mapped the enhancer and super-enhancer landscapes in antigen-specific naive, differentiated effector, and central memory CD8 T cells during LCMV infection. Epigenomics-based annotation revealed a highly dynamic repertoire of enhancers, which were inherited, de novo activated, decommissioned and re-activated during CD8 T cell responses.