Key Highlights from Cell Journal in March 2021: Insights into SARS-CoV-2 Variants, Brain Evolution, and Immune Therapies

March 31, 2021 / Bioon --- As March 2021 draws to a close, what are the standout studies published in Cell this month that are worth learning from? The editor has compiled them for sharing with readers.

1.Cell: New Study Shows SARS-CoV-2 Variants B.1.351 and P.1 Evade Neutralizing Antibodies
doi:10.1016/j.cell.2021.03.036

Testing and vaccination are the cornerstones of humanity’s efforts to control the SARS-CoV-2 coronavirus pandemic. Although it has taken longer than many anticipated, it is widely believed that achieving protection through vaccination is only a matter of time. However, time is also working in favor of the virus, which has undergone multiple mutations. Notably, the B.1.1.7 variant from the United Kingdom, the B.1.351 variant from South Africa, and the P.1 variant from Brazil are spreading rapidly. These viral variants have acquired mutations in the so-called spike protein, a surface structure responsible for attaching to host cells. Meanwhile, the spike protein is also the primary target of the immune response. Antibodies generated during SARS-CoV-2 infection or following vaccination bind to the spike protein, thereby neutralizing the virus.

Image source: Cell, 2021, doi:10.1016/j.cell.2021.03.036.

In a new study, a research team led by Markus Hoffmann and Stefan Pöhlmann from the German Primate Center – Leibniz Institute for Primate Research, and Jan Münch from Ulm University Medical Center in Germany, discovered that the SARS-CoV-2 variants B.1.351 and P.1 are no longer inhibited by antibodies used for COVID-19 treatment. Furthermore, these variants are less efficiently neutralized by antibodies from convalescent patients and vaccinated individuals. Consequently, recovery from COVID-19 and vaccination may provide only incomplete protection against these viral variants. The relevant findings were published online on March 20, 2021, in the journal Cell, under the title “SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies”.

2.Cell: Human and Chimpanzee Brains “Seamlessly Switch” by Changing a Single Molecular Switch
doi:10.1016/j.cell.2021.02.050

One of the most distinctive features of humans as a species is brain enlargement. Compared with mice, the total number of neurons in the human brain has increased by a factor of 1,000, making it the largest among all primates and more than three times that of our close relatives, chimpanzees and gorillas. Since humans diverged from other great apes, the human brain has undergone rapid expansion, yet the mechanisms underlying this human-specific expansion remain unknown. Moreover, although we have gained considerable understanding of the mechanisms governing the evolutionary differences between primates and rodents, human-specific changes relative to other apes remain poorly understood.

Based on this, Professor Madeline A. Lancaster from the MRC Laboratory of Molecular Biology at the University of Cambridge led a team to investigate the developmental mechanisms driving evolutionary brain expansion by using brain organoids derived from human, gorilla, and chimpanzee cells. They discovered that neuroepithelial differentiation is a protracted process in apes, involving a previously unrecognized transitional state characterized by changes in cell shape. Furthermore, comparative RNA sequencing (RNA-seq) revealed differences in the expression dynamics of cell morphogenesis factors, including ZEB2, a known regulator of epithelial-mesenchymal transition. The related findings were recently published online in the journal Cell under the title “An early cell shape transition drives evolutionary expansion of the human forebrain.”

3.Cell: Engineered immune cells can target and inhibit cancer cell metastasis
doi:10.1016/j.cell.2021.02.048

In a recent study, scientists genetically engineered immune cells to precisely deliver anticancer signals to organs where cancer might spread. In mouse models, researchers found that treatment with these engineered cells effectively reduced tumor size and prevented cancer from spreading to other parts of the body. The study, led by scientists at the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), was published in Cell on March 24, 2021.

Image source: www.pixabay.com.

Rosandra Kaplan, M.D., of the NCI Center for Cancer Research, said, “This is a novel immunotherapy with the potential to become a treatment for metastatic cancer.”

4.Cell Interpretation: Scientists Poised to Develop Novel Targeted Therapies for Neurological Disorders by Leveraging the Human Gut Microbiome
doi:10.1016/j.cell.2021.02.009

When considering the causes of neurological disorders and their treatment, we typically focus on research targeting the brain; but is this truly the optimal approach or the only direction? Recently, a study published in the international journal Cell, titled “Dissecting the contribution of host genetics and the microbiome in complex behaviors,” reported that scientists from institutions including Baylor College of Medicine in the United States discovered that gut microbes may trigger certain symptoms associated with complex neurological disorders. Therefore, microbiome-based therapies hold promise for treating human neurological diseases in the future.

Researcher Mauro Costa-Mattioli stated that various abnormal behaviors in the host may be regulated by the interdependent interaction between the host's genes and its microbiome. Specifically, in mouse models of neurodevelopmental disorders, hyperactive behavior is controlled by the host's genetic characteristics, whereas social behavioral deficits are mediated by the gut microbiome. More importantly, from a therapeutic perspective, treatment with specific microbes that promote the production of certain compounds within the biopterin family in the gut, or treatment with a metabolically active biopterin molecule, can improve social behaviors but does not enhance motor activity.

5.Cell: New Study Reveals Phase Transition in Embryonic Tissue
doi:10.1016/j.cell.2021.02.017

When researchers at the Institute of Science and Technology Austria observed developing zebrafish embryos, they witnessed a sudden, dramatic change: within just a few minutes, the solid-like embryonic tissue turned into a liquid-like state. What causes this transition, and what role does it play in subsequent embryonic development? In a new multidisciplinary study, they found the answers, which could reshape our understanding of key processes in development and disease, such as tumor metastasis. The related findings were published online in the journal Cell on March 16, 2021, under the title “Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions.”

To gain deeper insights into how a tiny cluster of cells develops into complex systems, such as fish, humans, or animals as large as elephants, many scientists turn to the zebrafish (Danio rerio). It offers several advantages that make it one of the favorite model organisms for developmental biologists like Nicoletta Petridou. First, this small, striped fish completes its development within just a few days; its embryos develop externally and are transparent, allowing for clear visualization of every organ during development. While observing zebrafish embryos a few hours after fertilization, Petridou and her colleagues discovered in a previous study that the viscosity of embryonic tissue undergoes a sudden change—a measure of a tissue’s resistance to deformation. Petridou explained, “At this early stage, the tissue forming the embryo is very rigid, but suddenly, the viscosity drops tenfold, and the tissue flows very rapidly—it becomes liquid-like.”

6.Cell: Scientists Poised to Develop Novel Therapies for Allergies and Autoimmune Diseases!
doi:10.1016/j.cell.2021.02.027

Recently, a research report published in the international journal Cell revealed that scientists from institutions such as the Australian National University have discovered that a special function within the immune system may hold promise for treating allergic diseases like asthma and helping to block life-threatening allergic reactions. In the article, the researchers elucidated a natural mechanism that helps prevent the body from developing autoimmune diseases and allergies, a process driven by a specialized protein known as neuritin.

Professor Carola Vinuesa stated that we have now identified a highly intriguing mechanism in the human body that helps block the production of “rogue” antibodies responsible for triggering autoimmune diseases or allergies. For a long time, it has been well established that neuroligins play critical roles in the brain and the nervous system; however, we have now discovered abundant expression of neuroligins and their mechanisms of action within the immune system, which had not been described in previous biological studies.

7.Cell: Why Do Single-Gene Mutations Make Certain Populations More Susceptible to Mycobacterial Diseases?
doi:10.1016/j.cell.2020.10.046

Recently, a research report titled “Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria,” published in the international journal Cell, revealed how rare mutations in patients help elucidate mysteries surrounding mycobacteria. Scientists from institutions including Rockefeller University demonstrated through their research that mere exposure to pathogens does not necessarily lead to disease. Interestingly, researchers have found that genetic factors play a critical role in determining whether pathogen exposure ultimately results in severe illness, as seen in conditions such as influenza, warts, and COVID-19.

Over the course of 25 years, researcher Jean-Laurent Casanova and colleagues have investigated the molecular mechanisms underlying the interaction between human genes and mycobacterial disease, continuing to conduct in-depth analyses of genetic defects to distinguish patients with severe infectious diseases from those who remain asymptomatic despite exposure to mycobacteria. In this study, the researchers reported their findings on a patient from Morocco suffering from severe mycobacterial disease.

8.Cell: Multiple SARS-CoV-2 Variants Can Resist Neutralizing Antibodies Induced by Pfizer and Moderna COVID-19 Vaccines
doi:10.1016/j.cell.2021.03.013

The SARS-CoV-2 coronavirus, which causes COVID-19, has undergone mutations throughout the pandemic. New variants of this virus have emerged worldwide, including those with potentially enhanced transmissibility or the ability to evade the immune system. Such variants have been identified in California (USA), Denmark, the United Kingdom, South Africa, and Brazil/Japan. Understanding how COVID-19 vaccines perform against these variants is critical to global efforts to curb the COVID-19 pandemic and is the focus of a new study from the Ragon Institute of MGH, MIT, and Harvard and Massachusetts General Hospital.

Image source: Cell, 2021, doi:10.1016/j.cell.2021.03.013.

In this study, Dr. Alejandro Balazs, a core member of the Ragon Institute, found that the neutralizing antibodies induced by the Pfizer and Moderna COVID-19 vaccines showed significantly reduced efficacy against SARS-CoV-2 variants first identified in Brazil/Japan and South Africa. Leveraging their experience in measuring HIV-neutralizing antibodies, Balazs and his team developed similar assays for COVID-19 to compare the effects of vaccine-induced neutralizing antibodies on the original strain versus the new variants. The relevant findings were published online in the journal Cell on March 12, 2021, under the title “Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity”.

9.Cell: Eight Ways Environmental Pollutants Harm the Body
doi:10.1016/j.cell.2021.01.043

A new review paper synthesizing existing evidence proposes eight characteristics of environmental exposures that delineate the biological pathways through which pollutants cause disease: oxidative stress and inflammation, genomic alterations and mutations, epigenetic alterations, mitochondrial dysfunction, endocrine disruption, altered intercellular communication, changes in microbiome communities, and impaired nervous system function. This review was recently published in the journal Cell under the title “Hallmarks of environmental insults.”

“Every day, we learn more about how exposure to pollutants in air, water, soil, and food harms human health. However, less is known about the specific biological pathways through which these chemicals cause damage to our bodies. In this review article, we provide a framework for understanding why complex mixtures of environmental exposures can lead to serious diseases, even at relatively moderate concentrations,” said Dr. Andrea Baccarelli, senior author of the paper and Chair of Environmental Health Sciences at Columbia University Mailman School of Public Health.

10.Cell: New Study Reveals That Atherosclerosis Accelerates the Generation of Clonal Hematopoiesis
doi:10.1016/j.cell.2021.01.049

In a new study, researchers from Massachusetts General Hospital (MGH) and Harvard Medical School now propose a different, additional possibility: atherosclerosis leads to clonal hematopoiesis. Patients with atherosclerosis suffer from hyperlipidemia and inflammation, both of which chronically enhance the division rate of hematopoietic stem cells. They confirmed that this increased division accelerates the generation of clonal hematopoiesis. The relevant findings were published online in the journal Cell on February 25, 2021, under the title “Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis”.

Dr. Kamila Naxerova, corresponding author of the paper and principal investigator at the Center for Systems Biology at Massachusetts General Hospital (MGH), stated, “Patients with atherosclerosis essentially experience ‘accelerated aging.’ This is because the rate at which genetic alterations arise and spread within the hematopoietic system is determined by the fundamental rate of stem cell division. From a genetic perspective, one could say that atherosclerosis accelerates the aging of blood. Given that clonal hematopoiesis is an age-related condition, patients with atherosclerosis are prone to earlier onset compared to healthy individuals.” (Bioon.com)