That's Good Science® Thursdays

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That's Good Science!

2021 research highlights

Good science comes in many shapes and styles. Takara Bio wants to celebrate recent achievements, publications, and discoveries from scientists around the globe. In That's Good Science Thursdays, Takara Bio reviews one publication per week. Let's change the world—together—one experiment at a time.

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Publication of the week

Researchers at City of Hope National Medical Center employed single cell transcriptomic profiling (scRNA-seq) performed on the ICELL8 system to examine the evolutionary trajectories of early stage breast cancer tumors using serial tumor biopsies from a clinical trial of preoperative endocrine therapy (letrozole) alone or in combination with the cell cycle inhibitor ribociclib. Their findings could potentially help optimize dosing and timing of combination therapies to counter treatment resistance in ER+ breast cancer. Read now »

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Oct. to Nov. July to Sept. Apr. to June Jan. to Mar.

Oct. to Nov.

October

October 21, 2021

SARS-CoV-2 infection produces varying degrees of illness. One serious response is multisystem inflammatory syndrome in children (MIS-C), a severe, uncontrolled inflammatory response involving multiple organs. Researchers at Cedars-Sinai Medical Center used various approaches including RNA-seq and BCR repertoire analysis to identify which factors lead to severe prognosis. The authors identified a strong autoimmune signature in MIS-C involving multiple pathogenic pathways. Read now »

October 14, 2021

Researchers at the Helmholtz Pioneer Campus developed snRNA-seq2, an improved single-nucleus RNA-seq (snRNA-seq) method for nuclear transcriptome analyses from frozen, archived liver samples. Using this new method, the authors characterize the transcriptomes of individual hepatocytes with different levels of ploidy. They demonstrate that while hepatocytes in young mouse livers express stem cell markers regardless of ploidy, hepatocytes with different levels of ploidy adjust their gene dosage according to their position in the liver. Read now »

October 7, 2021

Researchers from Fred Hutchinson Cancer Research Center comprehensively characterized escape, breadth and potency across a panel of SARS-CoV-2 antibodies and identified neutralizing antibodies with exceptional sarbecovirus breadth and resistance to SARS-CoV-2 escape. Read now »

July to Sept.

September

September 30, 2021

SARS-CoV-2 infects cells by a two-step process: first by interaction of its Spike protein with the ACE2 receptor on airway lining, then by cleavage of Spike by host proteases. Researchers at the University of Pittsburgh hypothesized that inhibition of TMPRSS2, a protease known to act in the second step, could work as a therapy against COVID-19. They performed a high-throughput screen of 2560 FDA-approved compounds at physiologically relevant concentrations and identified two that significantly reduce both TMPRSS2 expression and viral entry in cells. Read now »

September 23, 2021

Regulation of mitochondrial DNA (mtDNA) is carried out in part by TOP1MT, a topoisomerase found only in mitochondria. Researchers at the University of Calgary investigated two potentially pathogenic TOP1MT variants identified in a newborn with hypertrophic cardiomyopathy. The reduced functionality of both compound heterozygous variants shed light on TOP1MT’s role in regulating mitochondrial function. Learn how the group performed long-range PCR using Takara Bio's LA Taq Polymerase to identify deletions in full-length mtDNA templates. Read now »

September 16, 2021

To understand the mechanisms behind the neurological symptoms associated with “long-COVID”, Yang, Fabian, and colleagues assessed the transcriptional signature of COVID-19-affected brains using single-nuclei RNA-seq (snRNA-seq). Although they find no evidence that SARS-CoV-2 enters the brain, their data suggest that peripheral inflammation is relayed to brain cells, triggering neuroinflammation—and provides a molecular framework for COVID-19 neurological disease. Read now »

September 9, 2021

γδ T cells are critical during protective and destructive immunity, however, how they are functionally programmed remains unclear. Using transgenic mouse models, researchers from the University of Toronto studied the roles of ontogenic timing, TCR signal strength, and Notch signaling in γδ T cell functional differentiation in vivo. Surprisingly, Notch signaling was found to be dispensable for peripheral γδ T cell IL-17 production. Strong TCR signals, together with Notch, were found to promote IL-4 differentiation. Conversely, weaker TCR signals were seen to promote Notch-independent IL-17 differentiation. Altogether, the results precisely define the roles of functional programming in γδ T cell development. Read now »

September 2, 2021

Since the development of an effective screening system and prophylactic vaccines against oncogenic human papillomaviruses (HPVs), the incidence of uterine cervical cancer (UCC) has drastically decreased in most developed western countries. However, the same can’t be said for the rest of the world where UCC continues to be a major public health problem. To investigate the potential of developing precision medicine in the future, researchers from the National Cancer Center Research Institute (Tokyo, Japan) performed somatic genetic alteration analysis for post-hysterectomy high-risk early-stage UCC patients who underwent postoperative radiation therapy. Read now »

August

August 26, 2021

In the never-ending quest to better understand the immune system and its cells, this week’s paper focuses on neutrophils. Neutrophils are innate immune cells with two main functions: elimination of pathogens and inducing adaptive immune responses. However, how these cell types behave in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses, particularly related to HIV, are not well understood. In this paper, the authors elucidated how different neutrophil subtypes behave and their ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. With additional analysis, they also were able to understand the role Nβ and Nα play in the body. Read now »

August 19, 2021

Surveillance of emerging and circulating variants is crucial for tracking COVID-19 transmission. Researchers at the University of Southern California developed CorvGenSurv (Coronavirus Genomic Surveillance), a streamlined, high-resolution, and cost-effective SARS-CoV-2 whole genome sequencing method in which viral RNA is directly amplified, indexed, and sequenced. PrimeSTAR GXL DNA Polymerase powered the reactions by accurately amplifying long and complex RT-PCR products. This alternative to more common short-read sequencing approaches can facilitate widespread efforts to detect new mutations. CorvGenSurv therefore provides a vital tool to guide vaccination strategies and public health decision making. Read now »

August 12, 2021

Researchers from the Kanazawa Medical University, Japan developed a novel sequencing-based phase analysis method to distinguish between in cis and in trans heterozygous mutations using direct adapter ligation library preparation and paired-end sequencing. The authors validated their workflow by successfully elucidating two in trans compound heterozygous mutations in the ATP7B gene in a patient with Wilson’s disease—a rare, genetic disorder characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. Read now »

July

July 29, 2021

Researchers at the Fred Hutchinson Cancer Research Center developed the Multiple Target Identification by Tagmentation (MulTI-Tag) method on the ICELL8 Single-Cell System. This multifactorial profiling approach can detect and compare distinct chromatin-associated proteins within the same sample and is optimized to retain high sensitivity and specificity for multiple chromatin targets within the same cell. Read now »

July 22, 2021

Metagenomic analyses are important throughout the process of microbiome-based product development; however, standardization of these complex methodologies is lacking in this industry. Researchers at the Japan Microbiome Consortium (JMCB) and the National Institute of Advanced Industrial Science and Technology (AIST) used a mock microbiome to compare 11 library prep kits, pinpoint sources of bias, and establish standards for metagenomics of human fecal samples in the microbiome industry. Read now »

July 15, 2021

Could aberrant DNA methylation cause neuronal differentiation defects in Prader-Willi syndrome (PWS)? In a new study, Soeda et al. examined the ability of PWS patient-derived iPSCs (iPWS) to differentiate into neurons. Whether the iPWS carried a deletion or had methylation defects, they exhibited defective differentiation into ectoderm. The methylation-defective iPWS gave rise to fewer neural stem cells (NSCs), fewer mature neurons, and showed reduced expression of neural stem cell markers, including Pax6. Methylation is proposed to control neural differentiation through regulation of genes in the PWS region on chromosome 15. Read now »

July 8, 2021

Researchers at the Allen Institute For Brain Science used high-sensitivity single-cell RNA-seq to derive a transcriptomic cell-type taxonomy revealing a comprehensive repertoire of glutamatergic and GABAergic neuron types. Read now »

July 1, 2021

To better understand the CD4/CD8 lineage choice, researchers from the MRC London Institute of Medical Sciences used an scRNA-seq approach to help elucidate patterns of coreceptor gene activity and the associated gene expression. Read now »

Apr. to June

June

June 24, 2021

The metabolite adenosine is often highly expressed in tumors and believed to be an immunosuppressive feature of the tumor microenvironment. Researchers at the Peter MacCallum Cancer Centre found that using CRISPR/Cas9 to knock out adenosine receptors in CAR-T cells significantly boosted this immunotherapy’s anti-tumor activity and improved survival in mice. Read now »

June 17, 2021

While effective for treating blood cancers, major obstacles exist in using CAR-T therapies against solid tumors. Researchers in the Doudna lab have developed a Cas9-VLP system that simultaneously delivers Cas9 RNPs and therapeutic transgenes to specific T cell populations—streamlining the complex immune cell engineering required for the generation of effective CAR-T therapies against additional cancer types. Read now »

June 10, 2021

Using combinatorial genome editing, scientists at St. Jude Children's Research Hospital have developed acute erythroid leukemia (AEL) preclinical models in mice, then, using single-cell RNA sequencing, have quantified numerous mutations phenotypically presenting AEL. With this knowledge, they can proceed to also test drug treatments based on known sensititivities to those mutational combinations. Read now »

June 3, 2021

Researchers from the RIKEN Cluster for Pioneering Research (CPR) have produced NanoSINC-seq, a novel nanopore sequencing workflow, to help study mRNA isoforms produced during alternative splicing at the single-cell resolution. Read now »

May

May 27, 2021

By combining machine learning approaches with AAV-based probes, researchers at Carnegie Mellon developed a new method for identifying cell type-specific enhancer sequences that will enable deeper study and more targeted manipulation of different cell types in the brain and beyond. Read now »

May 20, 2021

Researchers at Tsinghua University in Beijing profiled the viral RNA-host protein interactomes of RNA viruses SARS-CoV-2, Ebola virus, and Zika virus. They identified interaction patterns that suggest common as well as virus-specific host responses, which they demonstrated can be used for rapid and targeted antiviral drug discovery. Read now »

May 13, 2021

Insightful work from Zhao et al. showing transcriptome reprogramming rewires signaling pathways in drug-resistant, aggressive mantle cell lymphoma (MCL). Using genomic, chemical proteomic, and drug screen profiling, they identified common pathways associated with treatment-resistant evolution of cancer cells. Read now »

May 6, 2021

By mRNA sequencing of patient-derived colorectal cancer (CRC) cultures at the single-cell level, researchers at the Heidelberg and German Cancer Research Center defined cell type-associated subpopulations with tumor-initiating cell (TIC) activity driving cancer progression and therapy resistance. Read now »

April

April 29, 2021

Researchers at Kyoto University describe an improved method to produce differentiated T cells from induced pluripotent stem cells. Read now »

April 15, 2021

Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Read now »

April 8, 2021

Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis. Read now »

April 1, 2021

SARS-CoV-2 ORF6 disturbs nucleocytoplasmic trafficking to advance the viral replication. Read now »

Jan. to Mar.

March

March 25, 2021

Revealing the human mucinome. Read now »

March 18, 2021

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality. Read now »

March 11, 2021

Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality. Read now »

March 4, 2021

sncRiboTag-Seq: cell-type-specific RiboTag-Seq for cells in low abundance in mouse brain tissue. Read now »

February

February 25, 2021

LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate. Read now »

February 18, 2021

Modular vaccine platform based on the norovirus-like particle. Read now »

February 11, 2021

40 minutes RT-qPCR assay for screening spike N501Y and HV69-70del mutations. Read now »

February 4, 2021

Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Read now »

January

January 28, 2021

Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Read now »

January 21, 2021

Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer. Read now »

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