Every species, including germs and people, has the ability to regenerate. Regeneration is controlled by the molecular mechanisms that change gene expression to control tissue renewal, repair, and growth.
The Department of Biomedical Engineering and the College of Medicine at Texas A&M University worked together to find out how important minerals are in controlling gene expression. Gene expression controls how many proteins a cell should make, which helps tissue grow back and changes a cell’s identity.
Future studies will build on this work to determine the functions of particular minerals and how they might be combined to create the next iteration of mineral medicines to repair injured tissue.
Science Advances recently published this study.
A large number of the body’s biological processes are regulated by minerals, which are inorganic substances that interact with vitamins, enzymes, hormones, and other nutrient cofactors. Even though it has been shown that some minerals affect how genes are expressed and how cells work, not much research has been done to figure out the molecular pathways involved.
Dr. Irtisha Singh, assistant professor in the Department of Molecular and Cellular Medicine at Texas A&M, and Dr. Akhilesh Gaharwar, associate professor of biomedical engineering and Presidential Impact Fellow, are the co-corresponding authors of the study in which a new class of mineral-based nanoparticles has been introduced to direct human stem cells toward bone cells. The team was able to determine the function of minerals in influencing gene expression profiles to guide stem cell differentiation using these nanoparticles, which are known as nanosilicates.
These nanosilicates are mineral nanoparticles with a diameter of 20–30 nanometers (nm) and a thickness of 1–2 nm. Due to their great biocompatibility, these nanoparticles are easily ingested by cells. Once these nanoparticles get into the cell body, they slowly break down into minerals like silicon, magnesium, and lithium.
Inside the cells, nanosilicates separate into separate minerals and activate a group of crucial genes that cause signaling pathways, or the flow of information between cells. These signaling pathways tell the cells what to do, like change into other types of cells or start the healing process by releasing extracellular matrix, a group of proteins that are specific to each type of tissue.
These extracellular matrices are made up of proteins like glycoproteins and proteoglycans, which help keep tissues working and help them heal.
The lead authors of this study, doctoral students Anna Brokesh and Lauren Cross, identify and characterize significant genes that are activated by various signaling pathways as a result of treatment with minerals by combining interdisciplinary techniques, biomedical engineering, and genomics methods. One of the study’s key results is that minerals like silicon, magnesium, and lithium have a role in endochondral ossification, the process by which stem cells in young people develop into soft and hard tissues like cartilage and bone.
Singh’s laboratory uses high-throughput functional tests and perturbations to analyze the functional regulatory systems in mammalian cells.
In order to assess the impact of nanosilicates and ionic dissolution products on the gene expression profiles of stem cells, researchers in this study used whole transcriptome sequencing (RNA-seq) data. RNA-seq, a high-throughput sequencing experiment that looks at the whole transcriptome, gives an objective and thorough review of the gene expression profiles. This helps find pathways that are changed by certain treatments.
Although there is no data to show how minerals affect us at the cellular level, many individuals are interested in learning how they affect the human body. “Our study is one of the first to look into how mineral ions can control the fate of stem cells. We did this by using unbiased transcriptome-wide sequencing.”
The suggested method resolves an issue that has long plagued current therapeutic strategies that use supraphysiological dosages of growth factors to guide tissue research. The side effects of such a high growth factor dosage include uncontrolled tissue growth, inflammation, and tumorigenesis, which is the production or development of tumor cells. The use of growth factors as a therapeutic agent in the field of regenerative medicine is adversely affected by these.
Gaharwar said that this research is important in a wide range of ways because it could lead to the development of new, therapeutically useful treatments for drug delivery, immunomodulation, and regenerative medicine.
This study was paid for by the National Institute of Neurological Disorders and Strokes, the Texas A&M University President’s Excellence Fund, and the National Institute of Biomedical Imaging and Bioengineering.
Graduate researchers Anna L. Kersey and Aparna Murali, undergraduate researcher Christopher Richter, and Dr. Carl Gregory, an associate professor of molecular and cellular medicine at the College of Medicine, are other authors of this work.
