The research team led by Professor Tang Zhouping from Tongji Hospital, affiliated with Tongji Medical College of Huazhong University of Science and Technology (HUST), published their findings in Signal Transduction and Targeted Therapy on July 30. The study is the first to demonstrate that a novel combination of small-molecular compounds can induce the direct conversion of astrocytes into electrophysiologically functional neurons in the pathological microenvironment of intracerebral hemorrhage.

Cerebral hemorrhage causes extensive neuronal death and triggers astrocyte proliferation, which leads to the formation of glial scars, thereby hindering neural repair. Tang Zhouping’s team pioneered an innovative formula, DFGKLRV, composed of seven types of small-molecular compounds.

Animal experiments showed that continuous localized infusion of this formula can achieve in situ reprogramming of astrocytes into neurons. Using transgenic mouse lineage-tracing technology, the researchers also confirmed that the newly generated neurons originated from astrocytes.

The study further revealed that ferroptosis significantly reduces the efficiency of this reprogramming process. To address this, the team creatively incorporated the ferroptosis inhibitor Ferrostatin-1 (Fer-1) into the formula, which downregulated the TGF-β/SMAD3/SOX9 signaling pathway, enhancing the efficiency of astrocyte-to-neuron conversion.

Compared with gene-editing approaches, small-molecule drugs pose no risk of genomic integration, offering higher safety and greater potential for clinical translation. This research identifies ferroptosis as a critical target for regulating chemical reprogramming. The team will continue optimizing the drug formula and exploring non-invasive delivery methods to advance the application of this technology, paving the way for new therapeutic strategies to address neurological damage after cerebral hemorrhage.

This achievement marks a significant milestone for the team, which has been dedicated to advancing stroke therapy and neural repair over the years. The team has established an innovative chain encompassing fundamental research, technological breakthroughs, clinical translation, and industrial incubation. Numerous research outcomes have been published in international journals such as The Lancet, and several core patents have been successfully converted into applications. The team has also helped incubate tech innovation companies focusing on brain-machine interfaces. To date, their work has earned multiple national and provincial-level science and technology awards and has been applied in over 200 tertiary class-A hospitals across China.

Source: Tongji Hospital of Tongji Medical College, HUST