Organoids-on-chips is opening up new frontier of research in biomedical field by combining organoids and organs-on-chips technology. The integrative technology offers great opportunities to maximize the potentials of organoids with higher fidelity, thus building advanced organ model systems in a physiologically relevant manner. In this review, we highlight the key features of organoids-on-chips and how this integrative technology could be used to build organoids in higher fidelity under controlled cellular microenvironment. We then introduce the recent progress of organoids-on-chips and their applications in biomedical research. We also discuss the opportunities and challenges of the nascent field of organoids-on-chips that lie ahead to accelerate their utility in disease research, drug testing, and regenerative medicine.
To date, over 170 different kinds of chemical modifications on RNAs have been identified, some of which are involved in multiple aspects of RNA fate, ranging from RNA processing, nuclear export, translation, and RNA decay. m6A, also known as N6-methyladenosine, is a prominent internal RNA modification that is catalyzed primarily by the METTL3-METTL14-WTAP methyltransferase complex in higher eukaryotic mRNA and long noncoding RNA (lncRNA). In recent years, abnormal m6A modification has been linked to the occurrence, development, progression, and prognosis of the majority of cancers. In this review, we provide an update on the most recent m6A modification discoveries as well as the critical roles of m6A modification in cancer development and progression. We summarize the mechanisms of m6A involvement in cancer and list potential cancer therapy inhibitors that target m6A regulators such as “writer” METTL3 and “eraser” FTO.
Parthenogenetic embryos derive their genomes entirely from the maternal genome and lack paternal imprint patterns. Many achievements have been made in the study of genomic imprinting using human parthenogenetic embryonic stem cells (hPg-ESCs). However, due to developmental defects and ethical limits, a comprehensive understanding of parthenogenetic embryonic development is still lacking. Here, we generated parthenogenetic blastoids (hPg-EPSCs blastoids) from hPg-ESC-derived extended pluripotent stem cells (hPg-EPSCs) using our previously published two-step induction protocol. Morphology, specific marker expression and single-cell transcriptome analysis showed that hPg-EPSCs blastoids contain crucial cell lineages similar to blastoids (hBp-EPSCs blastoids) generated from human biparental EPSCs (hBp-EPSCs). Single-cell RNA-seq compared the expression of genes related to imprinting and X chromosome inactivation in hPg-EPSCs blastoids and hBp-EPSCs blastoids. In conclusion, we generated parthenogenetic blastoids, which will potentially promote the study of genomic imprinting in embryonic development and uncover the influence of parental origin bias on human development and pathological mechanisms.
Metformin (MET) and nicotinamide riboside (NR) have both been reported to exert geroprotective effects in multiple species. However, the mechanism by which MET and NR regulate the aging program and delay aging in multiple tissues remains unclear. Here, we demonstrated that MET and NR attenuate aging features in human mesenchymal stem cells. Moreover, by systematically investigating the pathophysiological changes in different tissues from aged rats after oral administration of MET and NR, we showed that both MET and NR treatment alleviated various aging-related characteristics in multiple tissues, including inflammation, fibrosis, and protein aggregates. Consistently, MET or NR treatment partially rescued aging-related gene expression changes in aged rats. Collectively, we report that both MET and NR attenuate senescence phenotypes in human stem cells in vitro and in a variety of rodent tissues in vivo, thus providing a valuable resource and foundation for further evaluation of these two compounds against aging.