(Press-News.org) How do we become a complex, integrated multicellular organism from a single cell?
While developmental biologists have long researched this fundamental question, Stanford University biologist and HHMI investigator Dominique Bergmann's recent work on the plant Arabidopsis thaliana has uncovered surprising answers.
In a new study, published April 5 in Developmental Cell, led by Bergmann and postdoctoral scholar Camila Lopez-Anido, researchers used single-cell RNA sequencing technologies to track genetic activity in nearly 20,000 cells as they formed the surface and inner parts of an Arabidopsis leaf. Through this highly detailed technique, the researchers captured transient and rare cell states and found a surprising abundance of ambiguity in how cells traversed various identities, particularly early on within the stem cell population.
"All the cells are coordinated, and yet they're all individuals with their own genetic programs," said Bergmann, who is the Shirley R. and Leonard W. Ely, Jr. Professor in the School of Humanities and Sciences and senior author of the study. "And so we're really working to appreciate that balance between seeing what's new and special and unique about each one while also recognizing how they are working together."
While many scientists in this field focus on fruit flies and roundworms, some aspects of biological development will only be understood by studying other organisms - such as the plant Arabidopsis thaliana, which is the Bergmann lab's specialty.
"As we think about flexibility and resilience in the face of a changing world, we want to learn more about how organisms can manage to build functional bodies when they are under stress or exposed to extreme environments," said Lopez-Anido, who is lead author of the study. "This requires research with organisms that have flexible and tunable lifestyles, such as the plants we study."
As part of a family of artists, Lopez-Anido also embraced a uniquely artistic perspective to interpret and share this research. Within the paper itself, she used a pointillism-inspired analysis software to elegantly organize and visualize her massive dataset. Additionally, her sister, artist Virginia Lopez-Anido, created artwork inspired by Camila's research, which will be featured on the cover of Developmental Cell.
Surprising details
While previous experiments on Arabidopsis had worked out some of the important genes and steps in making specialized cells, this new cell-by-cell data fills in additional details of development. The researchers found, for example, that cells might double-back on the developmental path they seemed to be following, and that it was also possible to jump ahead. They also noticed that there may be differences in the way new stem cells regulated transitions between cell types relative to old stem cells; and whereas they had previously known of core steps in cell differentiation, they saw there were actually many small, seemingly continuous steps along the way.
One especially intriguing finding concerns a crucial gene, called SPEECHLESS, that plays a role in the formation of pores, called stomata, through which the plant exchanges gases and regulates water content. The Bergmann lab has studied SPEECHLESS extensively, but the new data hinted that it was expressed for a longer stretch of the developmental process than they expected. In a follow-up experiment, the researchers were able to selectively remove the gene after it completed its known role but sooner than the new data said it was done being expressed. Sure enough, the developmental programs went off track - and the researchers are now working to figure out why.
"It was a contradiction of what we thought we knew and it was really exciting," Bergmann said. "It makes us want to dig in to other unexpected details - what might look like insignificant blips in the data - and see what we've missed."
Bergmann credits Lopez-Anido and this work with inspiring several avenues of research, including reconsidering what it means to be a stem cell, reframing events that define final differentiation stages and reevaluating what it means to be born as a cell on the top versus bottom of a leaf.
Art, science and mentorship
Analyzing cell identities from nearly 20,000 cells - and 30,000 genes - required machine learning algorithms. So, Lopez-Anido created an organizational framework built around one of the most widely used analysis tools, which is called Seurat after pointillist painter Georges Seurat. As in pointillism, individual dots, which represented individual cells and their specific gene expression signatures, blended together in visualizations that enabled the researchers to see large-scale trends.
Virginia Lopez-Anido visualized Camila's work in another way. She developed a drawing series on the nature of scientific inquiry (Untitled, pencil on paper, 8.5 x 11.7in, 2021), as well as a clay model series of tissue landscapes inspired by scanning electron microscope images of stomata (Untitled, digital photograph, 2021), which is the art that will grace the cover of Developmental Cell.
"I like to engage with artists and scholars across disciplines because it can bring new layers of meaning to science - and make science more accessible, which is very important to me," said Camila Lopez-Anido, who has taught scientific literacy at Bard College through their Citizen Science program and will soon begin work as an assistant professor of biology at Reed College. "I'm looking forward to fostering more of these meaningful research experiences and collaborations for my mentees."
INFORMATION:
Additional co-authors on this paper include former postdoctoral scholar Anne Vatén, research assistant N. Katherine Smoot, research scientist Nidhi Sharma, PhD student Yan Gong, former research assistants Maria Ximena Anleu Gil and Victoria Guo and former postdoctoral scholar Annika Weimer. Bergmann is also a member of Stanford Bio-X and the Stanford Cancer Institute.
This research was funded by the National Institutes of Health, EMBO and The German Research Foundation. Bergmann is an investigator of the Howard Hughes Medical Institute, which also provided funding for this research.
PHILADELPHIA - A team led by scientists at the Perelman School of Medicine at the University of Pennsylvania has illuminated the functions of mysterious structures in cells called "nuclear speckles," showing that they can work in partnership with a key protein to enhance the activities of specific sets of genes.
The discovery, which will be published on April 5 in Molecular Cell, is an advance in basic cell biology; the key protein it identifies as a working partner of speckles is best known as major tumor-suppressor protein, p53. This avenue of research may also lead to a better future understanding of cancers, and possibly better cancer treatments.
"This study shows that nuclear speckles work as major regulators of gene expression, and suggests that ...
UNIVERSITY PARK, Pa. -- Approximately 40,000 children in the United States may have lost a parent to COVID-19 since February 2020, according to a statistical model created by a team of researchers. The researchers anticipate that without immediate interventions, the trauma from losing a parent could cast a shadow of mental health and economic problems well into the future for this vulnerable population.
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Research from Northwestern Medicine shows nearly two-thirds of males and more than one-third of females with one or more existing psychiatric disorders when they entered detention, still had a disorder 15 years later.
The findings are significant because mental health struggles add to the existing racial, ethnic and economic disparities as well as academic challenges from missed school, making a successful transition to adulthood harder to attain.
"Kids get into trouble during adolescence.Those from wealthier families also use drugs and get into fights. But these situations are most often ...
What The Study Did: Researchers estimated and projected the number of children in the United States affected by the death of a parent from COVID-19.
Authors: Rachel Kidman, Ph.D., of Stony Brook University in Stony Brook, New York, is the corresponding author.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamapediatrics.2021.0161)
Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.
INFORMATION:
Media advisory: The full study is linked to this news release.
Embed this link to provide your readers ...
CLAREMONT, CA - Keck Graduate Institute (KGI) Assistant Professor and University of California, Berkeley Visiting Scientist Dr. Kiana Aran first introduced the CRISPR-Chip technology in 2019. Now just two years later, she has expanded on its application to develop CRISPR-SNP-Chip, which enables detection of single point mutations without amplification in Sickle Cell Disease and Amyotrophic lateral sclerosis (ALS).
"The field of CRISPR-based diagnostics is rapidly evolving due to CRISPR programmability and ease of use," Aran says. "However, the majority of CRISPR-based diagnostics platforms are still relying on target amplifications or optical detections. The reprogrammability of CRISPR combined with optics-free highly scalable graphene transistors will allow us to bring the ...
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A RMIT-led team has now introduced ultrathin beta-tellurite to the two-dimensional (2D) semiconducting material family, providing ...
Irvine, Calif. -- In 2019, the National Weather Service in Alaska reported spotting the first-known lightning strikes within 300 miles of the North Pole. Lightning strikes are almost unheard of above the Arctic Circle, but scientists led by researchers at the University of California, Irvine have published new research in the journal Nature Climate Change detailing how Arctic lightning strikes stand to increase by about 100 percent over northern lands by the end of the century as the climate continues warming.
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An interdisciplinary team led by KU Leuven and Stanford has identified 76 overlapping genetic locations that shape both our face and our brain. What the researchers didn't find is evidence that this genetic overlap also predicts someone's behavioural-cognitive traits or risk of conditions such as Alzheimer's disease. This means that the findings help to debunk several persistent pseudoscientific claims about what our face reveals about us.
There were already indications of a genetic link between the shape of our face and that of our brain, says Professor Peter Claes from the Laboratory for Imaging Genetics at KU Leuven, who is the joint senior author of the study with Professor Joanna Wysocka from the ...
Journal Name: Nature Methods
Title of the Article: Discovering multiple types of DNA methylation from individual bacteria and microbiome using nanopore sequencing
Corresponding Author: Gang Fang, PhD
Bottom Line:
Bacterial DNA methylation occurs at diverse sequence contexts and plays important functional roles in cellular defense and gene regulation. An increasing number of studies have reported that bacterial DNA methylation has important roles affecting clinically relevant phenotypes such as virulence, host colonization, sporulation, biofilm formation, among others.
Bacterial methylomes contain three ...
What The Study Did: A clinical risk assessment tool developed in China was tested with a group of patients in Spain to evaluate its ability to predict critical illness among patients hospitalized with COVID-19 in Europe.
Authors: Oscar Moreno-Perez, M.D., Ph.D., of the Alicante General University Hospital-Alicante Institute of Sanitary and Biomedical Research in Alicante, Spain, is the corresponding author.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamainternmed.2021.0491)
Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and ...
