When a sheep loses its tail, it cannot regenerate it in the manner of lizards. On the other hand, it is possible to clone mammals from somatic cells, showing that a complete developmental program is intact in a wounded sheep's tail the same way it is in a lizard. Thus, there is a requirement for more than only the presence of the entire genetic code in somatic cells for regenerative abilities. Thoughts like this have motivated us to assemble more than just a factographic synopsis on tissue regeneration. As a model, we review skin wound healing in chronological order, and when possible, we use that overview as a framework to point out possible mechanisms of how damaged tissues can restore their original structure. This article postulates the existence of tissue structural memory as a complex distributed homeostatic mechanism. We support such an idea by referring to an extremely fragmented literature base, trying to synthesize a broad picture of important principles of how tissues and organs may store information about their own structure for the purposes of regeneration. Selected developmental, surgical, and tissue engineering aspects are presented and discussed in the light of recent findings in the field. When a sheep loses its tail, it cannot regenerate it in the manner of lizards. On the other hand, it is possible to clone mammals from somatic cells, showing that a complete developmental program is intact in a wounded sheep's tail the same way it is in a lizard. Thus, there is a requirement for more than only the presence of the entire genetic code in somatic cells for regenerative abilities. Thoughts like this have motivated us to assemble more than just a factographic synopsis on tissue regeneration. As a model, we review skin wound healing in chronological order, and when possible, we use that overview as a framework to point out possible mechanisms of how damaged tissues can restore their original structure. This article postulates the existence of tissue structural memory as a complex distributed homeostatic mechanism. We support such an idea by referring to an extremely fragmented literature base, trying to synthesize a broad picture of important principles of how tissues and organs may store information about their own structure for the purposes of regeneration. Selected developmental, surgical, and tissue engineering aspects are presented and discussed in the light of recent findings in the field.
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http://dx.doi.org/10.1203/PDR.0b013e31816a7453 | DOI Listing |
Genomics Proteomics Bioinformatics
January 2025
Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.
Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome.
View Article and Find Full Text PDFThe current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers.
View Article and Find Full Text PDFHead and neck squamous cell carcinoma (HNSCC) develops and advances because of the accumulation of somatic mutations located in orthosteric and allosteric areas. However, the biological effects of allosteric driver mutations during tumorigenesis are mostly unknown. Here, we mapped somatic mutations generated from 10 tumor-normal matched HNSCC samples into allosteric sites to prioritize the mutated allosteric proteins via whole-exome sequencing and AlloDriver, identifying the specific mutation H351Q in β-glucuronidase (GUSB), a lysosomal enzyme, as a novel allosteric driver mutation, which considerably encouraged HNSCC progression both in vitro and in vivo.
View Article and Find Full Text PDFBackground: Megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare and progressive neurodegenerative disorder involving the white matter, is not adequately recapitulated by current disease models. Somatic cell reprogramming, along with advancements in genome engineering, may allow the establishment of human models of MLC for disease modeling and drug screening. In this study, we utilized cellular reprogramming and gene-editing techniques to develop induced pluripotent stem cell (iPSC) models of MLC to recapitulate the cellular context of the classical MLC-impacted nervous system.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biological Sciences, Indian Institute of Science Education and Research Berhampur, India. Electronic address:
Long Interspersed Nuclear Element 1 (LINE1/L1) retrotransposons, which comprise 17% of the human genome, typically remain inactive in healthy somatic cells but are reactivated in several cancers. We previously demonstrated that p53 silences L1 transposons in human somatic cells, potentially acting as a tumor-suppressive mechanism. However, the precise molecular mechanisms underlying p53-mediated repression of L1 and its life cycle intermediates remain unclear.
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