Significance: The architecture of the mitochondrial network and cristae critically impact cell differentiation and identity. Cells undergoing metabolic reprogramming to aerobic glycolysis (Warburg effect), such as immune cells, stem cells, and cancer cells, go through controlled modifications in mitochondrial architecture, which is critical for achieving the resulting cellular phenotype. Recent Advances: Recent studies in immunometabolism have shown that the manipulation of mitochondrial network dynamics and cristae shape directly affects T cell phenotype and macrophage polarization through altering energy metabolism. Similar manipulations also alter the specific metabolic phenotypes that accompany somatic reprogramming, stem cell differentiation, and cancer cells. The modulation of oxidative phosphorylation activity, accompanied by changes in metabolite signaling, reactive oxygen species generation, and adenosine triphosphate levels, is the shared underlying mechanism. Critical Issues: The plasticity of mitochondrial architecture is particularly vital for metabolic reprogramming. Consequently, failure to adapt the appropriate mitochondrial morphology often compromises the differentiation and identity of the cell. Immune, stem, and tumor cells exhibit striking similarities in their coordination of mitochondrial morphology with metabolic pathways. However, although many general unifying principles can be observed, their validity is not absolute, and the mechanistic links thus need to be further explored. Future Directions: Better knowledge of the molecular mechanisms involved and their relationships to both mitochondrial network and cristae morphology will not only further deepen our understanding of energy metabolism but may also contribute to improved therapeutic manipulation of cell viability, differentiation, proliferation, and identity in many different cell types. Antioxid. Redox Signal. 39, 684-707.

• Klíčová slova
• cristae, metabolic reprogramming, mitochondrial dynamics,
• MeSH
• energetický metabolismus MeSH
• glykolýza MeSH
• metabolické sítě a dráhy MeSH
• mitochondriální dynamika * MeSH
• mitochondrie * metabolismus   MeSH
• oxidativní fosforylace MeSH
• přeprogramování buněk MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches.

• Klíčová slova
• Genetic engineering, induced pluripotency, nuclear reprogramming, regenerative medicine, somatic cell nuclear transfer, stem cells.,
• MeSH
• genetické inženýrství MeSH
• indukované pluripotentní kmenové buňky metabolismus   cytologie   MeSH
• lidé MeSH
• přeprogramování buněk * MeSH
• regenerativní lékařství * MeSH
• tkáňové inženýrství MeSH
• vývojová biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The authors of the article titled "Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine" (Dhanjal DS, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K, Chopra C. Curr Med Chem. 2024; 31(13): 1646-1690. DOI: 10.2174/0929867330666230503144619. PMID: 37138422) [1] have made revisions to the references in the text and the reference section. These updates have been made to ensure the integrity of the article. The updated reference list can be found in the latest version of the article. The authors apologize for any confusion or inconvenience caused. The original article can be found online at: https://www.eurekaselect.com/article/131443.

• MeSH
• lidé MeSH
• přeprogramování buněk * genetika   MeSH
• regenerativní lékařství * MeSH
• vývojová biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

DNA damage can result from intrinsic cellular processes and from exposure to stressful environments. Such DNA damage generally threatens genome integrity and cell viability1. However, here we report that the transient induction of DNA strand breaks (single-strand breaks, double-strand breaks or both) in the moss Physcomitrella patens can trigger the reprogramming of differentiated leaf cells into stem cells without cell death. After intact leafy shoots (gametophores) were exposed to zeocin, an inducer of DNA strand breaks, the STEM CELL-INDUCING FACTOR 1 (STEMIN1)2 promoter was activated in some leaf cells. These cells subsequently initiated tip growth and underwent asymmetric cell divisions to form chloronema apical stem cells, which are in an earlier phase of the life cycle than leaf cells and have the ability to form new gametophores. This DNA-strand-break-induced reprogramming required the DNA damage sensor ATR kinase, but not ATM kinase, together with STEMIN1 and closely related proteins. ATR was also indispensable for the induction of STEMIN1 by DNA strand breaks. Our findings indicate that DNA strand breaks, which are usually considered to pose a severe threat to cells, trigger cellular reprogramming towards stem cells via the activity of ATR and STEMINs.

• MeSH
• listy rostlin genetika   růst a vývoj   MeSH
• mechy genetika   růst a vývoj   MeSH
• meristém genetika   růst a vývoj   MeSH
• poškození DNA fyziologie   MeSH
• přeprogramování buněk genetika   MeSH
• proliferace buněk MeSH
• zvětšování buněk * MeSH
• Publikační typ
• časopisecké články MeSH

Aim: Human induced pluripotent stem cells (iPSCs) are inefficiently derived from somatic cells by overexpression of defined transcription factors. Overexpression of H2A histone variant macroH2A1.1, but not macroH2A1.2, leads to increased iPSC reprogramming by unclear mechanisms. Materials & methods: Cleavage under targets and tagmentation (CUT&Tag) allows robust epigenomic profiling of a low cell number. We performed an integrative CUT&Tag-RNA-Seq analysis of macroH2A1-dependent orchestration of iPSCs reprogramming using human endothelial cells. Results: We demonstrate wider genome occupancy, predicted transcription factors binding, and gene expression regulated by macroH2A1.1 during reprogramming, compared to macroH2A1.2. MacroH2A1.1, previously associated with neurodegenerative pathologies, specifically activated ectoderm/neural processes. Conclusion: CUT&Tag and RNA-Seq data integration is a powerful tool to investigate the epigenetic mechanisms occurring during cell reprogramming.

• Klíčová slova
• CUT&Tag, iPSCs, induced pluripotent stem cells, macroH2A1, reprogramming, somatic cells,
• MeSH
• endoteliální buňky metabolismus   MeSH
• histony * metabolismus   MeSH
• indukované pluripotentní kmenové buňky * metabolismus   MeSH
• lidé MeSH
• přeprogramování buněk genetika   MeSH
• sekvenování transkriptomu MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histony * MeSH
• transkripční faktory MeSH

MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem cells (iPSCs). We focused our investigations on miR-145 and showed that this candidate is highly expressed in DFs relative to iPSCs and significantly downregulated during reprogramming process. Inhibition of miR-145 in DFs led to the induction of "cellular plasticity" demonstrated by: (a) alteration of cell morphology associated with downregulation of mesenchymal and upregulation of epithelial markers; (b) upregulation of pluripotency-associated genes including SOX2, KLF4, C-MYC; (c) downregulation of miRNA let-7b known to inhibit reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the presence of reprogramming factors. Together, our results indicate a direct functional link between miR-145 and molecular pathways underlying reprogramming of somatic cells to iPSCs.

• Klíčová slova
• Induced pluripotent stem cells, KLF4, Mesenchymal-to-epithelial transition, OCT4, Reprogramming, SOX2, c-MYC, miR-145, microRNA,
• MeSH
• fibroblasty cytologie   metabolismus   MeSH
• indukované pluripotentní kmenové buňky cytologie   MeSH
• Krüppel-like faktor 4 MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• přeprogramování buněk * genetika   MeSH
• regulace genové exprese MeSH
• reprodukovatelnost výsledků MeSH
• sekvence nukleotidů MeSH
• škára cytologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• KLF4 protein, human MeSH Prohlížeč
• Krüppel-like faktor 4 MeSH
• mikro RNA MeSH
• MIRN145 microRNA, human MeSH Prohlížeč

Reprogramming to pluripotency is associated with DNA damage and requires the functions of the BRCA1 tumor suppressor. Here, we leverage separation-of-function mutations in BRCA1/2 as well as the physical and/or genetic interactions between BRCA1 and its associated repair proteins to ascertain the relevance of homology-directed repair (HDR), stalled fork protection (SFP), and replication gap suppression (RGS) in somatic cell reprogramming. Surprisingly, loss of SFP and RGS is inconsequential for the transition to pluripotency. In contrast, cells deficient in HDR, but proficient in SFP and RGS, reprogram with reduced efficiency. Conversely, the restoration of HDR function through inactivation of 53bp1 rescues reprogramming in Brca1-deficient cells, and 53bp1 loss leads to elevated HDR and enhanced reprogramming in mouse and human cells. These results demonstrate that somatic cell reprogramming is especially dependent on repair of replication-associated double-strand breaks (DSBs) by the HDR activity of BRCA1 and BRCA2 and can be improved in the absence of 53BP1.

• Klíčová slova
• BRCA1, BRCA2, CP: Molecular biology, double-strand break, pluripotency, replication gap suppression, replication stress, somatic cell reprogramming, stalled replication fork,
• MeSH
• 53BP1 * metabolismus   genetika   MeSH
• dvouřetězcové zlomy DNA * MeSH
• lidé MeSH
• myši MeSH
• oprava DNA * MeSH
• přeprogramování buněk * MeSH
• protein BRCA1 * metabolismus   genetika   MeSH
• rekombinační oprava DNA MeSH
• replikace DNA MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 53BP1 * MeSH
• BRCA1 protein, human MeSH Prohlížeč
• Brca1 protein, mouse MeSH Prohlížeč
• protein BRCA1 * MeSH
• TP53BP1 protein, human MeSH Prohlížeč
• Trp53bp1 protein, mouse MeSH Prohlížeč

The possibility of replacing the originally discovered and widely used DNA reprogramming transcription factors is stimulating enormous effort to identify more effective compounds that would not alter the genetic information. Here, we describe the generation of induced pluripotent stem cells (iPSc) from head-derived primary culture of mouse embryonic cells using small chemical inhibitors of the MEK and TGF-beta pathways without delivery of exogenous transcription factors. These iPSc express standard pluripotency markers and retain their potential to differentiate into cells of all germ layers. Our data indicate that head-derived embryonic neural cells might have the reprogramming potential while neither the same primary cells cultivated over five passages in vitro nor a cell population derived from adult brain possesses this capacity. Our results reveal the potential for small molecules to functionally replace routinely used transcription factors and lift the veil on molecular regulation controlling pluripotency. The conditions described here could provide a platform upon which other genome non integrative and safer reprogramming processes could be developed. This work also shows novel potential for developing embryonic neural cells.

• MeSH
• diferenciační antigeny biosyntéza   MeSH
• indukované pluripotentní kmenové buňky cytologie   metabolismus   MeSH
• MAP kinasový signální systém * MeSH
• myši MeSH
• přeprogramování buněk * MeSH
• transformující růstový faktor beta metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• diferenciační antigeny MeSH
• transformující růstový faktor beta MeSH

Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

• MeSH
• buněčné linie MeSH
• embryo savčí * MeSH
• fibroblasty cytologie   metabolismus   MeSH
• lidé MeSH
• mikro RNA * biosyntéza   genetika   MeSH
• oktamerní transkripční faktor 3 * biosyntéza   genetika   MeSH
• regulace genové exprese * MeSH
• techniky buněčného přeprogramování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA * MeSH
• oktamerní transkripční faktor 3 * MeSH
• POU5F1 protein, human MeSH Prohlížeč

The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Reprogramming is a process mediated by multiple factors, including oncogenes, growth factors, hypoxia-induced factors, and the loss of suppressor gene function, which support malignant transformation and tumor development in addition to cell heterogeneity. Consequently, this hallmark promotes resistance to conventional anti-tumor therapies by adapting to the drastic changes in the nutrient microenvironment that these therapies entail. Therefore, it represents a revolutionary landscape during cancer progression that could be useful for developing new and improved therapeutic strategies targeting alterations in cancer cell metabolism, such as the deregulated mTOR and PI3K pathways. Understanding the complex interactions of the underlying mechanisms of metabolic reprogramming during cancer initiation and progression is an active study field. Recently, novel approaches are being used to effectively battle and eliminate malignant cells. These include biguanides, mTOR inhibitors, glutaminase inhibition, and ion channels as drug targets. This review aims to provide a general overview of metabolic reprogramming, summarise recent progress in this field, and emphasize its use as an effective therapeutic target against cancer.

• Klíčová slova
• carbohydrates, energy metabolism, immunotherapy, inflammation, metabolic reprogramming, neoplasms, tumor microenvironment,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH