Wednesday, April 09, 2025

Researchers unveil evolutionary conservation and innovation in mammalian hypothalamus development

Chinese Academy of Sciences Headquarters

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Principles of Hypothalamic Development and Evolution Across Species
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Credit: IGDB

The hypothalamus is a small but critical region at the base of the brain that controls the autonomic nervous system, regulates body temperature, signals hunger and thirst, exerts hormonal control over the pituitary gland, helps set circadian rhythms, influences sexual behavior and reproduction, and plays a role in instinctive behaviors like fear, aggression, and maternal bonding.

Despite its compact size, it features a remarkably complex structure and function, along with an extremely diverse array of neuronal types. While much is known about brain regions like the cerebral cortex and cerebellum, the developmental mechanisms and evolutionary adaptations of the mammalian hypothalamus have remained elusive.

In a new study published in Developmental Cell on April 8, a research team led by Prof. WU Qingfeng at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences has demonstrated the conserved cellular development and evolutionary innovations in the developing human hypothalamus.

The mammalian brain develops through a sophisticated, choreographed series of genetically regulated events: shaping distinct neural progenitor (early brain cell) domains, producing neurons from neural progenitors, establishing connections between neurons, and fine-tuning their communications. While the hypothalamus follows a similar blueprint, it takes a unique developmental detour to be able to accomplish its diverse functions.

Previously, WU and his team proposed a "cascade diversifying model" to explain how the hypothalamus generates its extraordinary neuronal diversity. They showed that neural progenitors, intermediate progenitors, and nascent neurons along the lineage hierarchy contribute to the fate diversification of hypothalamic neurons in a stepwise fashion.

In this new study, WU's team closely examined how brain cells in the hypothalamus are organized during development, traced how different types of cells emerge from neural progenitors as the brain grows, and identified which genetic features have been conserved across mammals—and which ones have uniquely changed in humans over the course of evolution.

This study advances our understanding of how the hypothalamus develops by making three types of contributions: methodological, resource-related, and conceptual. On the methodological side, the researchers combined several advanced techniques—single-cell analysis, single-nucleus sequencing, and spatial transcriptomics—to get a detailed view of gene activity during brain development. As a resource, they used these data to create a spatial map showing where different neural progenitor cells are located in the developing mammalian hypothalamus. For the conceptual contribution, they identified three conserved morphogenetic centers (called "tertiary organizers") that send out signals to coordinate early hypothalamic regionalization, revealing an anteroposterior segmentation of the hypothalamic primordium by the FOX gene family. These findings provide key mechanistic insights into the neural patterning process governing human and mouse hypothalamus development.

The team then used computational methods to reconstruct a neurogenic lineage tree, tracing how different types of hypothalamic neurons develop from various progenitor regions. They identified a set of conserved lineage factors that may guide this developmental process. In addition, they discovered a distinct neuronal subtype unique to humans, whose function is not yet known, and they observed a substantial increase in the expression of neuromodulatory genes—such as those coding for ion channels, receptors, and neuropeptides—in human neurons.

Spatial mapping revealed that neuroendocrine neurons—specifically, the GnRH and GHRH types—are distributed differently in humans compared to mice. This suggests that the structure and function of the neuroendocrine system have evolved differently in each species to meet their unique needs.

In addition, a cross-species comparison of hypothalamic dopamine neurons provided proof-of-concept evidence for a potential shift in dual-transmitter co-transmission (dopamine-GABA and dopamine-glutamate) and peptide-neurotransmitter couplings (dopamine-AVP and dopamine-GHRH) across species.

These divergences may contribute to phenotypic differences between species, such as evolutionary changes in reward learning, motivated behavior, body growth pattern, and stress response. To support these findings, the researchers developed machine learning frameworks for lineage reconstruction and regulatory network inference, backed by multi-species transcriptomic datasets.

Collectively, this study reveals conserved neural patterning mechanisms in mammalian hypothalamus development, reconstructs a neurogenic lineage tree, and identifies four adaptive evolutionary divergences in developing human neurons: a human-enriched neuronal subtype, enhanced neuromodulation, redistributed neuroendocrine neurons, and reconfigured neurochemistry in hypothalamic dopamine neurons.

This work presents the first integrative analysis of cellular ontogeny and evolutionary divergence in the developing mammalian hypothalamus. The comprehensive findings suggest that human subcortical structures may generally adopt conserved neural patterning strategies, while adapting neuronal composition, spatial distribution, input sensitivity, and stability of neural output to support advanced social cognition and behavioral flexibility.

The innovation among hypothalamic neurons revealed in this study will enhance our understanding of the cellular mechanisms underlying human-specific physiological functions and disease vulnerabilities.

Journal

Developmental Cell

DOI

10.1016/j.devcel.2025.03.009

Article Title

Transcriptional conservation and evolutionary divergence of cell types across mammalian hypothalamus development

Article Publication Date

8-Apr-2025

PCORI commits to new patient-centered CER to empower health care decisions

Funding awards for new patient-centered CER address a range of pediatric and adult health challenges

Patient-Centered Outcomes Research Institute

PCORI commits to new patient-centered CER to empower health care decisions — image:
The Patient-Centered Outcomes Research Institute (PCORI) has announced funding for new patient-centered comparative clinical effectiveness research (CER) studies across a range of conditions. These studies will help provide patients and caregivers with the evidence needed to make more informed health and health care decisions and more effectively manage their health.
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Credit: Patient-Centered Outcomes Research Institute

April 8, 2025

WASHINGTON, D.C. — Every day, millions of Americans make health care decisions without enough information to fully understand the trade-offs between approaches to care and make informed choices for themselves or their families. To help address these information gaps, the Patient-Centered Outcomes Research Institute (PCORI) has announced funding for new patient-centered comparative clinical effectiveness research (CER) studies across a range of conditions. These studies will help provide patients and caregivers with the evidence needed to make more informed health and health care decisions and more effectively manage their health.

Research Funding Highlights

Sixteen new patient-centered CER studies addressing a range of health challenges
Among the CER studies, eight focused on long-term follow-up of patient-centered health outcomes
Six additional health research studies focused on CER methods and engagement in science

The newly awarded patient-centered CER studies include research comparing:

Two durations of antibiotics for children hospitalized with common infections
Treatments for neurodevelopmental differences in young children
Interventions to treat pediatric anxiety
Mammography with and without artificial intelligence assistance
Care approaches for rare diseases such as spina bifida and amyotrophic lateral sclerosis

Eight of the patient-centered CER studies will examine the long-term effects of treatments, interventions and programs previously studied in PCORI-funded CER, aiming to provide a more comprehensive understanding of the potential benefits and harms of these approaches.

Additional research awards support four studies to improve patient-centered CER methods and two studies to strengthen the evidence base on effectively engaging patients and other health and health care decisionmakers through the design and conduct of patient-centered CER.

Accelerating uptake of PCORI-funded research results

PCORI also supports initiatives to accelerate the implementation of PCORI-funded CER results into clinical practice, addressing the often-cited 17-year gap between result publication and clinical practice adoption.

Through its Health Systems Implementation Initiative (HSII), PCORI has announced 19 funding awards focused on:

Improving hypertension diagnosis and management
Electronic monitoring of patient-reported outcomes during cancer treatment
Optimizing outpatient antibiotic prescribing for children with acute respiratory tract infections (ARTIs)

With these new awards, HSII participant health systems have implementation projects across 31 states and the District of Columbia. These projects have the potential to impact care for 1.9 million patients across 3,800 care sites and include previously awarded PCORI-funded projects for intensive lifestyle treatment programs for weight loss as well as additional awards to improve antibiotic prescribing for children with ARTIs.

See the full list of new research and HSII awards on PCORI’s website.

All award funding has been approved pending final PCORI contractual considerations.

With the latest funding awards through the Patient-Centered Outcomes Research Institute's Health Systems Implementation Initiative, 31 health systems are implementing findings of PCORI-funded comparative clinical effectiveness research (CER) studies to improve care for adults and children across the nation.

Credit

Patient-Centered Outcomes Research Institute

About PCORI

The Patient-Centered Outcomes Research Institute (PCORI) is a nonprofit organization authorized by Congress to fund patient-centered comparative clinical effectiveness research (CER). CER compares two or more health care options, generating evidence about any differences in potential benefits or harms to empower patients, caregivers and other health care decision makers with information to make informed choices that reflect their needs and preferences. PCORI emphasizes the engagement of patients, caregivers and the broader health care community in all aspects of PCORI-funded research and research-related activities, including the dissemination and uptake of research findings.

Chinese researchers boost efficiency of direct methanol fuel cell catalysts

Chinese Academy of Sciences Headquarters

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Schematic illustration of ultrafine Pt-based ultrafine high-entropy octahedra and performance testing
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Credit: ZHANG's group

Replacing traditional fossil fuels with clean, renewable energy sources is expected to solve environmental issues and alleviate the energy crisis. As a novel energy conversion device, fuel cells are capable of efficiently transforming chemical energy into electrical energy.

Methanol, a liquid fuel known for its high energy density, safety, and ease of transport, has long been seen as a promising candidate for fuel cells. However, a major challenge in methanol oxidation is the rapid deactivation of catalysts caused by poisoning species formed during the reaction. These species—especially carbon monoxide—stick to catalysts and keep them from working. Therefore, enhancing the activity and anti-poisoning performance of the catalyst is key to developing direct methanol fuel cells (DMFCs).

In response to this challenge, a research team led by Prof. ZHANG Tierui from the Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences (CAS) has developed a new catalyst that significantly enhances the efficiency and durability of methanol oxidation reactions. Composed of ultrafine platinum-based high-entropy alloy (HEA) octahedra, the catalyst marks a promising advance in DMFC efficiency and resistance to catalytic poisoning.

This breakthrough was published in Matter on April 8.

Due to the exposed crystal facets of Pt-based octahedral materials, they have shown good activity in various electrocatalytic reactions. However, the high surface energy of these nano-octahedra cause them to be unstable and prone to aggregation. As a result, it is difficult to efficiently use the catalyst’s active sites.

In this study, Prof. ZHANG's team addressed the challenge by engineering ultrafine HEA octahedra composed of multiple metal elements. By incorporating a diverse set of elements, the researchers successfully reduced the surface energy of platinum-based nano-octahedra, enabling the formation of stable structures with edge lengths under 3 nanometers—significantly smaller than those achieved in earlier efforts.

The experimental results show that as the number of metal elements increases, the size of the octahedra gradually decreases. For example, the average edge length of this senary alloy—one comprising six different metal elements—is only 2.8 nanometers.

Electrochemical tests and theoretical calculations indicate that the synergistic effect of multiple metal elements further modulates the electronic structure of platinum (Pt). In the methanol oxidation reaction, the senary alloy outperformed both ternary alloys—alloys comprising three metal elements—and commercial platinum-on-carbon (Pt/C) catalysts in terms of activity and resistance to poisoning.

This work was supported by the National Key Projects for Fundamental Research and Development of China, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and the Youth Innovation Promotion Association of CAS.