Nicotine exposure during pregnancy increases flu severity later in life

University of California - Santa Cruz

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Credit: CDC/ Debora Cartagena

Exposure to nicotine during pregnancy and shortly after birth can have a lasting impact on a child’s immune system and cause more severe respiratory infections later in life, shows a new study from researchers at the University of California, Santa Cruz. 

Prenatal nicotine exposure has long been known to cause a range of health issues, from premature birth to increased respiratory illnesses, but scientists have not clearly understood the processes that cause these vulnerabilities. Now, research published in Stem Cell Reports shows that in mice models, nicotine exposure during pregnancy and just after birth alters the stem cells that create the body’s blood cells and other crucial lung immune cells. This leads to increased susceptibility and severity to influenza, and likely other respiratory diseases, later in life. 

"This study is not on all the compounds you inhale while smoking a cigarette, it is really on the addictive compound nicotine,” said Marcel Rommel, a study author and postdoctoral researcher at UC Santa Cruz. “During pregnancy, clinicians sometimes recommend nicotine replacement therapy, such as patches or gum, to help patients quit smoking. These products still contain nicotine, and our study suggests that nicotine itself negatively affects the development of the immune system.”

Isolating nicotine’s impact

This research was led by Professor of Biomolecular Engineering Camilla Forsberg’s lab at the Institute for the Biology of Stem Cells (IBSC) and the Baskin School of Engineering. The lab focuses on blood stem cell development and disease from embryonic development to aging, and the impact of environmental exposures, positive or negative, on blood system health throughout life. 

Cigarettes, other tobacco products, and newer alternatives such as vapes and nicotine pouches, contain nicotine alongside other potentially harmful substances, making it difficult to separate nicotine’s effects from those of other ingredients. Supported by funding from the UC tobacco-related disease research program, the researchers decided to look at the impact of nicotine on its own, particularly as nicotine is consistently the addictive compound found in more modern tobacco products as cigarette use declines. 

“We want to translate the research that we do in the lab to people's well-being,” said Alessandra Rodriguez y Baena, study author, Forsberg lab Ph.D. alumna, and a current biology professor at Hartnell College. “In the U.S., almost 4% of mothers smoke during pregnancy, and in other countries there are still a lot more than that. Most people know that smoking during pregnancy is harmful, but we still have much to learn about how nicotine affects a developing baby and whether those effects can last into adulthood.”

The researchers used mouse models and cell lineage-tracing tools to understand the effects of perinatal nicotine exposure to blood-forming stem cells, which are crucial to the immune system.

They found that offspring exposed to nicotine were born with fewer blood-forming stem cells, called hematopoietic stem cells (HSCs). These cells showed altered patterns of immune regulator genes, which persisted into adulthood, even though nicotine exposure ended shortly after birth.

“These cells are reduced after exposing these mice to nicotine, which could be a reason why epidemiological studies have shown that children are more susceptible to respiratory tract infections,” Rommel said. “This could tell us why—it’s really an impact in the cellular space. Even more than just being exposed to smoke, it might be the nicotine received during pregnancy.”

Long term effects

Into adulthood, the changes in blood cells appeared to be reduced. However, their lungs had fewer resident macrophages, the key immune cells that essentially clean up the lungs and act as a first line of defense against pathogens. 

“HSCs exposed to nicotine during embryonic development end up being diminished, and we're not specifically sure why, but there's a change in a different direction than if you expose the mice to nicotine during adulthood,” said Taylor Cool, who started the project as a Ph.D. student in the Forsberg lab and is now a program manager at the UC Santa Cruz IBSC. “Adult HSCs respond differently than fetal HSCs, which is really interesting.”

Although adult HSC seemed to rebound into adulthood, further testing showed that heightened disease severity appears to be a lasting impact of nicotine exposure. The researchers tested the impact of an influenza infection on the nicotine-exposed mice, in collaboration with members of UC Santa Cruz Assistant Professor of Molecular, Cell, and Developmental Biology David Boyd’s lab, which studies respiratory viral infections. 

During influenza infection, they found increased inflammation in the lungs and greater movement of immune cells to this area, which led to more severe lung damage and greater weight loss. This supports the idea of cellular memory—that a primary exposure to something trains the immune system positively or negatively, and impacts secondary exposures later in life. 

“Cells can have this memory, but don’t show it, until the second hit,” Rommel said. “We want to follow up on this—what is this memory, and where is it in the cells?”

The researchers anticipate that a similar exaggerated response would be seen with other respiratory viruses or bacterial infections, like pneumonia or RSV. Taken together, the researchers hope that this study might offer support for protective public health measures.

“Our findings suggest that the environment we are exposed to early in life can have lasting effects on the immune system,” Rodriguez y Baena said. “We studied influenza, which we can get vaccinated against. So the next question is, ‘Can we reduce the harmful effects of these early exposures through public health measures?’ Understanding these early exposures can help us find ways to protect people later in life from the consequences of exposures they had no control over.” 

This study unfolded over more than five years, guided by the ranging and interdisciplinary expertise of researchers at the Forsberg lab and at UC Santa Cruz. 

“This project is a really good example of how different perspectives and researchers’ experiences can help guide the next questions,” Rodriguez y Baena said. “We did experiments, we let the data tell its story, but then the next questions we were able to ask because of the multiple people that were participating in that project and their own experiences.”

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Journal

Stem Cell Reports

DOI

10.1016/j.stemcr.2026.103118

Article Title

Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Severity in Adulthood

Article Publication Date

15-Oct-2026

Early nicotine exposure leaves a lasting effect on the immune system

International Society for Stem Cell Research

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Nicotine exposure during pregnancy and shortly after birth caused lasting changes to the blood-forming stem cells and the developing immune system in mice, including a more damaging response to influenza infection later in life, researchers found.

The research team, led by Camilla Forsberg at the University of California, Santa Cruz, USA, exposed pregnant mice to nicotine to investigate the effects of perinatal nicotine exposure (PNE) to the blood building system. The researchers found that offspring exposed to nicotine had fewer blood-forming stem cells, the cells that produce mature effector immune cells and altered patterns of immune regulatory genes within these cells. These changes persisted into adulthood, even though nicotine exposure ended shortly after birth. The findings were published today in Stem Cell Reports.

The immune damage was largely invisible under normal conditions in adult mice. Exposed mice had normal numbers of immune cells circulating in their blood. However, their lungs had fewer resident macrophages,, immune cells that provide an important first line of defense against pathogens. When the PNE mice were later infected with influenza virus, their immune systems responded with increased inflammation and greater movement of immune cells into the lungs. This heightened response resulted in more severe lung damage and greater weight loss.

“This shows how sensitive the developing blood system is to its environment.” said Marcel Rommel, Ph.D. “Blood stem cells set the balance of the immune system, and they carry a memory of what they encountered early in life. An exposure in the first weeks of life can tip that balance in a way that stays hidden until the body faces an infection, and that shapes immune health well into adulthood. The best protection is avoiding nicotine during pregnancy, but we also want to understand whether these changes can be counteracted once they have occurred.”

Smoking during pregnancy is known to negatively affect fetal development, including development of the immune system. Children born to mothers who smoke during pregnancy, for example, are more likely to experience respiratory infections, which can also be more severe.

Tobacco smoke contains many harmful substances in addition to nicotine, making it difficult to determine the effects of nicotine alone. This study helps address that question by isolating nicotine exposure in a mouse model. The findings suggest that nicotine itself can disrupt immune development and have effects that persist long after exposure ends.

“What happens during early development can shape health for a lifetime,” said Taylor Cool, Ph.D. “Our findings show how perinatal nicotine exposure can permanently alter the stem cells responsible for building the immune system. Our study highlights how exposure during this critical window can have lifelong consequences for health.”

While findings in mice do not necessarily translate directly to people, the research raises important questions about nicotine exposure during pregnancy and early development, including through products such as e-cigarettes and nicotine replacement therapies.

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Stem Cell Reports is a Cell Press partner journal. Find the journal on X: @StemCellReports.

About ISSCR
Across more than 80 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to advancing stem cell research and its translation to medicine.

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Journal

Stem Cell Reports

DOI

10.1016/j.stemcr.2026.103118

Article Title

Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Severity in Adulthood

Article Publication Date

15-Oct-2026

 

Exercise is good for us—but why?

Salk Institute researchers introduce a molecular atlas of exercise-associated changes in mice, defining the healthy, exercised-trained state, which could help improve performance and prevent injury

Salk Institute

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Manoj Hariharan (left), Geraldine Maier (center), and Ramesh Ramasamy (right) debuted a molecular atlas of exercise-associated changes in mice, defining the healthy, exercised-trained state, which could help improve performance and prevent injury.

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Credit: Salk Institute

LA JOLLA (October 15, 2026)—To understand what goes wrong in the body, scientists must first know what right looks like. Salk Institute researchers are building a scientific reference, piece by piece, for what makes a body healthy. Their latest effort maps how exercise reshapes the body at the molecular level, examining responses across organs, cell types, sexes, and circadian phases in mice.

The result is a first-of-its-kind molecular atlas spanning 22 tissues and integrating bulk RNA sequencing, metabolomics, proteomics, single-nucleus RNA sequencing, and DNA methylation profiling. The researchers uncovered distinct responses to exercise that vary by tissue, cell type, sex, and circadian categories. By defining a healthy baseline, the atlas gives scientists a starting point to explore how tissues adapt to exercise, work toward more personalized exercise strategies, and identify new molecules and pathways for further investigation.

The study was published in Cell on October 15, 2026, and was funded by both federal research grants and private philanthropy.

What do we know about exercise?

It’s no surprise that exercise is good for you—we hear it all the time. Exercise can make us resilient against disease and dysfunction, speed up recovery from illness, and reduce mortality overall. In fact, studies have linked exercise to more than 30 percent lower all-cause, cardiovascular, and cancer mortalities.

Despite knowing all the good that exercise can do, scientists have had a hard time deciphering why. This question has been difficult to answer, in part because studies in humans are limited to blood and a few muscles. As a result, mouse models have become a popular tool for determining the molecular signatures of exercise.

The Salk research team compared young male and female mice that either spent eight weeks running voluntarily on a wheel or were sedentary. They collected 22 tissue samples, during both active and resting time of the day.

“Exercise doesn’t just change our muscles, it changes many of our organs and cells at different levels—some short-term, some long-term,” says co-first and co-corresponding author Geraldine Maier, PhD, a staff scientist at Salk. “Our experimental setup allows us to capture that detail across tissues, and sexes, and in muscle, down to the individual cell types.”

How do you build an exercise atlas?

After collecting various tissues from sedentary and running mice, the researchers started with bulk RNA sequencing on all 22 tissues. Bulk RNA sequencing reveals which genes are active in each tissue. Then, they conducted metabolomics on eight tissues and plasma, which catalogs the small molecules that cells use and produce by cellular metabolism. Next was proteomics, which measures the protein levels in a certain tissue—in this case, the researchers looked at four specific leg muscles (a hamstring muscle, two calf muscles, and quadriceps).

After discovering that leg muscles had the biggest responses to exercise at the whole-tissue level, they used single-cell RNA and DNA methylation in three leg muscles. Rather than generalizing over the whole tissue, single-cell inquiry provides specific detail that differentiates neighboring cells by their precise identities and activities.

The Salk study is the first to conduct single-cell methylation work on muscle after exercise. Methylation is a type of epigenetic change that regulates the expression of genes. Compared to differences in protein or RNA expression, exercise-induced changes in DNA methylation are more permanent. Methylation can lead to lasting regulatory changes that alter cell type and whole-tissue behavior.

In addition to creating the atlas, the researchers used the transcriptomic dataset to develop a 51-gene exercise signature that distinguishes exercise-trained from sedentary muscle in both mice and humans. This signature could help to identify biomarkers and study muscle disuse and dysfunction.

How does exercise change living systems, on a molecular scale?

The atlas first revealed that exercise induced widespread, tissue-specific cellular remodeling—with most transcriptional changes occurring in skeletal muscle. Exercise changed the activity of nearly half the genes in at least one tissue, yet no single gene’s activity was changed in all 22 tissues. And in muscle, exercise altered methylation in specific cell types but not others. These findings especially demonstrate the power of single-cell-level analyses, as these details would have been missed in bulk sequencing.

When looking at differences across circadian phases, the team noted that most tissues changed more during the active phase, excluding the hypothalamus, kidney, and lung. When looking at sex-based differences, females had broader transcriptional responses and distinct gene expression patterns compared to males. There was also a strong sex-specific epigenetic response to training.

“Our atlas provides a comprehensive resource for understanding the systemic molecular adaptations to endurance exercise,” says co-first author Ramesh Ramasamy, PhD, a former computational biologist at Salk. “Now that we have all this data, researchers can begin developing strategies that harness exercise—either alone or in combination with other interventions—to ensure we all live long, healthy lives.”

What can an exercise atlas be used for?

The atlas is a starting point toward creating exercise routines tailored to individuals, since responses differ by sex and time of day. It also provides the data needed for more targeted research within specific tissues and cell types, which could potentially point to new biomarkers or strategies for improving performance, recovery, and muscle health.

“Now that we have the data,” adds Maier, “labs can identify one gene or metabolic pathway they find interesting then dissect that mechanism. Our atlas gives the field a shared foundation to build on.”

“Exercise impacts the whole body, not just your muscles, so an atlas like ours that looks more holistically at many tissues is key to understanding the true impact of exercise,” says co-first author Manoj Hariharan, PhD, a former senior staff scientist at Salk. “That’s also why single-cell studies are so important—there are so many cell type-specific changes that get lost in bulk sequencing. I hope our work highlights that and encourages more single-cell atlases, and especially multi-omic single-cell atlases, moving forward.”

Further research will need to explore how “sticky” exercise-induced changes are. How long do you have to exercise to see lasting change? How long do those changes last? Do cells remember exercising after months? Years?

An atlas marks the beginning of an endeavor that can go on for decades. With new data come new questions and new discoveries, each bringing us closer to understanding human health and how we can protect it.

Other information and funding

The work was supported by the Wu Tsai Human Performance Alliance; Joe and Clara Tsai Foundation; National Institutes of Health (S10 OD026929, P30 014195, HG010634); Chapman Foundation; Helmsley Charitable Trust; Ministry of Education, Culture, Sports, Science and Technology in Japan; Veterans Administration; National Science Foundation (2138259, 2138286, 2138307, 2137603, 2138296); and Howard Hughes Medical Institute.

This press release was written by Isabella Davis.

Journal: Cell

Paper title: Multi-omics atlas of chronic exercise

DOI: 10.1016/j.cell.2026.09.044

About the Salk Institute for Biological Studies

The Salk Institute is an independent, nonprofit research institute founded in 1960 by Jonas Salk, developer of the first safe and effective polio vaccine. The Institute’s mission is to drive foundational, collaborative, risk-taking research that addresses society’s most pressing challenges, including cancer, Alzheimer’s disease, and crop resilience. This foundational science underpins all translational efforts, generating insights that enable new medicines and innovations worldwide. Learn more at www.salk.edu.

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Journal

Cell

DOI

10.1016/j.cell.2026.09.044

Article Title

Multi-Omics Atlas of Chronic Exercise

Article Publicatio

 

With a flick of a switch: Reducing addiction risk from opioid painkillers

Penn’s Dirk Trauner and collaborators have developed a platform that allows opioid activity to be turned ‘on’ or ‘off’ with the flick of a light switch, paving the way for bypassing opioid addiction and other adverse side effects

University of Pennsylvania

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Joshua Levitz (left), biochemistry and biophysics professor at Weill Cornell Medicine, and Dirk Trauner, the George A. Weiss University Professor and a Penn Integrates Knowledge Professor with joint appointments in the Department of Chemistry in the School of Arts & Sciences and the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine.

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Credit: University of Pennsylvania and Weil Cornell Medicine

Last year, more than 40,000 Americans died from overdoses involving opioids, according to the Centers for Disease Control and Prevention.

Opioid compounds, including morphine, codeine, and fentanyl, exert most of their effects by activating mu-opioid receptors, which are found throughout the brain and in the spinal cord, peripheral nerves, and gut. These compounds can be very potent painkillers, but their bodywide activity leads to side effects including constipation, tolerance (the need for higher and higher doses), addiction, and—potentially fatally—the suppression of brain signals that control breathing.

Eliminating or at least greatly reducing side effects would mean targeting the activity of opioid painkillers very selectively to the neurons or nerve fibers where they are needed.

In a new paper published in Cell, chemist and pharmacologist Dirk Trauner and collaborators at Weill Cornell Medicine and the University of Southern California present an experimental opioid painkiller designed to be reversibly switched “on” and “off” with different light frequencies to keep its action local and out of the brain. Their findings may eliminate the dangerous side effects that characterize current opioids.

“It would be terrible if we would deprive people suffering from debilitating pain from opioids, because they’re too important and effective for that,” says Trauner, a Penn Integrates Knowledge Professor in the School of Arts & Sciences and the Perelman School of Medicine. “Yet, you want to make them safer, and that’s our main goal here.”

The work builds on two decades of research in Trauner’s lab on controlling biology with light. In 2004, Trauner and colleagues at the University of California, Berkeley, used a synthetic azobenzene switch to turn the firing of neurons on and off with light.

The paper appeared months before a landmark study by Karl Deisseroth and colleagues that helped define and establish optogenetics, the use of light to control the activity of nerve cells—a field that was recognized with this year’s Nobel Prize in Physiology or Medicine. Trauner notes that the early history highlights the crucial role chemistry played in the field’s origins.

“The idea of light-switchable receptor activators has been around for 20 years or so, but I think these results represent a major step forward,” says study co-senior author Joshua Levitz, a professor of biochemistry and biophysics at Weill Cornell Medicine.

Creating a light switch

Using azobenzenes, organic compounds that can stably and reversibly change their shape when exposed to certain light frequencies, the team designed several morphine-azobenzene compounds that engage the mu-opioid receptor differently depending on the light to which they’ve been exposed.

One of these compounds, AM-3, worked just as they had hoped, activating the mu-opioid receptor strongly when in a shape induced by near-ultraviolet light but weakly when in a shape induced by blue light.

The researchers showed that with this “photopharmacology” approach, they could activate AM-3’s painkilling effect only where needed, allowing substantial pain relief without side effects such as tolerance or constipation in multiple preclinical pain models, including cancer pain models. AM-3 cannot cross into the brain easily, helping to minimize brain-based side effects such as addiction and respiratory suppression.

“We think this is a significant breakthrough not just for pain management but also for the general strategy of photopharmacology, which has a great many potential applications in biology and medicine,” says Levitz.

Looking ahead

The teams hope to take their approach through further preclinical development and ultimately to clinical trials. The researchers are working on successor molecules that are switchable with safer light frequencies than ultraviolet light, which can damage eyes and skin.

“Next is to make them adaptable for humans,” says Trauner. “Our goal is to make them sensitive toward long wavelengths like red light, which can deeply penetrate skin and tissue. We need to improve the photochemistry, but we have some pretty good ideas on how to do this. In fact, we have some exciting preliminary results already.”

Weill Cornell Medicine contributed to this news release.

Dirk Trauner is the George A. Weiss University Professor and a Penn Integrates Knowledge Professor with joint appointments in the Department of Chemistry in the School of Arts & Sciences and the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania.

Joshua Levitz is a professor of biochemistry and biophysics at Weill Cornell Medicine.

Other authors include Xiang Ji and Kenny Calderon-Godinez of Penn Arts & Sciences; Luca Posa, Giovanna R. Romano, Sheida Sharghi Moshtaghin, Anisul Arefin, Alberto J. Gonzalez-Hernandez, Ipsit Srivastava, and Kristen E. Pleil of Weill Cornell Medicine; Saif Khan, Antonina L. Nazarova, Gye Won Han, Saheem A. Zaidi, Zixin Zhang, Aaliyah S. Tyson, Mohsen Ranjbar, Vsevolod Katritch, and Cornelius Gati of the University of Southern California; Bruno Paz of New York University and the University of São Paulo; and Kanupriya Pande of Lawrence Berkeley National Laboratory.

This research was supported by the National Institutes of Health (grants R61/R33DA051529, R35GM150982, R01AT012075, R35GM153437, T32GM132081, and R36DA064987), the Rohr Family Research Scholar Award, the Monique Weill-Caulier Award, and the Charles H. Revson Fellowship.

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Journal

Cell

DOI

10.1016/j.cell.2026.09.042

Method of Research

Experimental study

Subject of Research

Animals

Article Title

An opioid efficacy switch for reversible optical control of analgesia

Article Publication Date

15-Oct-2026

COI Statement

L.P., G.R.R., V.K., D.T., and J.L. are inventors on a provisional patent application on the use of photoswitchable morphines for pain treatment.

 

In plants, sense of time is connected with sense of danger

Washington University in St. Louis

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Salty soil is a growing threat to crops worldwide. Hotter, drier weather has increased evaporation rates, drawing moisture from the soil and leaving behind concentrated mineral salts. At the same time, water shortages are forcing farmers to irrigate using water from lower-quality, saline or recycled sources. Scientists estimate that around half of the world’s irrigated farmland is now affected by salinity to some degree.

A new study from Washington University in St. Louis reveals how a plant’s internal clock helps it to respond to dangerous salts in its environment. Understanding how plants time their defenses against salt could eventually help scientists develop crops that hold up better against salt stress.

The research, published Oct. 14 in Science Advances, was led by biologist Xuehua Zhong, the Dean’s Distinguished Professorial Scholar in WashU Arts & Sciences, and WashU postdoctoral fellow Wenwen Tian, an expert in circadian biology.

Biologists already knew that a plant’s internal clock and its stress responses were connected — but not how the clock actually reaches the genes that protect the plant when trouble hits.

The link is surprisingly physical, Zhong said.

“When a plant senses salt, a clock protein clusters into tiny droplets inside the nucleus, which frees protective genes to switch on,” Zhong said. “Because the clock protein is part of this switch, the plant’s stress defenses are tied to its sense of time.”

Among the researchers’ findings:

• A critical clock protein reacts to salt. Originally discovered and extensively studied in the model plant Arabidopsis thaliana, a clock protein called TIC ensures that biological rhythms synchronize properly with the 24-hour day-and-night cycle. Zhong and Tian found that when a plant is exposed to salt, TIC quickly gathers into tiny droplets inside the cell nucleus. “It’s the first evidence that a clock component can respond directly to salt, linking the plant’s sense of time with its sense of danger,” Zhong said.
• Timing matters for survival. In this new study, plants that were modified to remove TIC were more vulnerable to salt. But these plants also had an internal clock that ran about 21 hours instead of 24. “When we grew them under 21-hour days that matched their clock, they actually handled salt better,” Zhong said. “This shows that a plant copes with stress best when its internal clock is in sync with the outside world.”
• Plants have a switch that turns on protective genes. As TIC droplets form, they pull on a group of enzymes that normally keep salt-protection genes turned down, Zhong said. With those enzymes partly out of the way, the genes switch on more strongly, helping the plant survive.

These findings open novel ways to think about building more resilient crops, the scientists said. Because TIC acts as a salt-responsive switch, it could become a target for breeding or gene editing. The new research also shows that plants cope with salt best when their internal clock matches their environment, a finding that suggests that tuning crop clocks could improve stress tolerance, Zhong said.

“The clock directly shapes stress responses,” said Zhong, who also credited WashU undergraduate researcher Xinheng Lyu and visiting Stanford undergraduate student Grace Qian for making important contributions to this research as co-authors. “The same stress can produce different gene expression outcomes depending on when it occurs.”

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Funding: Zhong’s research was supported in part with grants from the National Institutes of Health (R35GM124806) and the National Science Foundation (MCB-2448006), as well as other federal funding.

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Journal

Science Advances