A roundup of research articles published in the previous month (16 April 2023 – 15 May 2023) at the institute:
Transgenerational epigenetic inheritance: Is it harmful or beneficial?
The transfer of gene expression information without changing the sequence of DNA from one generation to another is known as epigenetic inheritance and is seen in the form of intergenerational and trans-generational inheritance. The mechanism and physiological relevance of these forms of inheritance is not yet fully understood.
In this paper, Abhay Sharma’s lab has shed light on the adaptive and maladaptive changes that transgenerational inheritance can lead to by using a combination of existing transcriptomics data from mice and drosophila studies followed by experimental validation in drosophila. The diet and temperature induced changes that are inherited have shown to cause dysregulation in the genes responsible for proteolysis. This has been found to be conserved between drosophila and mice.
Another interesting finding that has been reported is the change in the direction of phenotype, in terms of expression of a protein coding gene – if the expression was decreased in the parent, then it was found to be increased in the offspring. This change can be beneficial or harmful for the offspring depending on the conditions being different or similar as for the parental generation.
Phenotypic cross-species conservation and cross-generation directionality switching in epigenetic inheritance. Bhalla A, Sharma A. Mol Ecol. 2023 May 7. Online ahead of print.
Restoring intercellular mitochondrial transfer by mesenchymal stem cells
The use of mesenchymal stem cells for regenerative medicine has advanced in the last two decades. The cell based therapy has been replaced by harnessing of the secretory vesicles, cytokines and growth factors that are released by MSCs for therapeutic purposes. Healthy mitochondria have also been shown to be donated by MSCs to the dysfunctional cells known as intercellular mitochondrial transport.
One of the benefits of stem cell based therapy is the low risk of rejection in transplantation when using own stem cells. Currently, it is not known whether the presence of metabolic diseases can affect MSCs and the efficacy of MSC based therapies. Soumya Sinha Roy’s lab used an obesity model to identify whether MSCs get affected by disease conditions or not. It was found that these MSCs showed an inability to remove damaged mitochondria, impaired intercellular mitochondrial transport and reduced cardiolipin content.
They could restore the removal of defective mitochondria thereby increasing intercellular mitochondrial transport to dysfunctional cells and efficiency of MSC based therapy for asthma using a small antioxidant molecule PQQ. The findings were tested in an animal model of asthma where the dysfunctional lung epithelial cells could be restored into a healthy metabolic state.
Obesity impairs cardiolipin-dependent mitophagy and therapeutic intercellular mitochondrial transfer ability of mesenchymal stem cells. Sagar S, Faizan MI, Chaudhary N, Singh V, Singh P, Gheware A, Sharma K, Azmi I, Singh VP, Kharya G, Mabalirajan U, Agrawal A, Ahmad T, Sinha Roy S. Cell Death Dis. 2023 May 13;14(5):324.
Variants of the Human Platelet Antigens in the Indian population
Human platelets, the fragments of cells that help in blood clotting, are known to possess 41 antigens (glycoproteins in nature) and are known as human platelet antigens (HPA). The genetic diversity of these antigens is the reason for diseases and conditions like neonatal alloimmune thrombocytopenia and post transfusion complications. Additionally, HPAs have been implicated in cardiovascular diseases, interaction with malignant cells.
To understand the genetic diversity of HPA in the Indian population, the previously generated IndiGen database of 1029 healthy individuals was analyzed and the frequency of the various alleles were found. Genetic landscape of human platelet antigen variants in the Indian population analysed from 1029 whole genomes. Rophina M, Bhoyar RC, Imran M, Senthivel V, Divakar MK, Mishra A, Vatsyayan A, Jolly B, Sivasubbu S, Scaria V. Int J Immunogenet. 2023 Jun;50(3):134-143. Epub 2023 May 9.