Rationale: Demyelination is a major component of white matter injury, characterized by oligodendrocyte (OL) death and myelin sheath loss, which result in memory loss and cognitive impairment in the context of ischemic stroke. Accumulating evidence has shown that OLs can be generated by the direct activation of defined transcription factors (TFs) in human induced pluripotent stem cells (hiPSCs); however, the rapid acquisition of single TF-induced OL progenitor cells (OPCs) as cell therapy for ischemic stroke remains to be thoroughly explored.

Vitamin A is essential for brain function, in addition to its important roles in vision, immunity, and reproduction. Previous studies have shown that retinoic acid (RA), the bioactive form of vitamin A, is involved in the regulation of various intracellular responses related to biological rhythms. RA is reported to affect the circadian rhythm by binding to RA receptors, such as receptors in the circadian feedback loops in the mammalian suprachiasmatic nucleus. However, evidence of the impacts of vitamin A deficiency (VAD) on biological rhythms is limited, and most of the related studies were conducted on animals. In this review, we described the physiological functions of biological rhythms and physiological pathways/molecular mechanisms regulating the biological rhythms. We then discussed the current understanding of the associations of VAD with biological rhythm disorders/diseases (sleep disorders, impairments in learning/memory, emotional disorders, and other immune or metabolism diseases) and summarized the currently proposed mechanisms (mainly by retinoid nuclear receptors and related proteins) for the associations. This review may help recognize the role of VAD in biological rhythm disorders and stimulate clinical or epidemiological studies to confirm the findings of related animal studies.

Transcription factors (TFs) have been introduced to drive the highly efficient differentiation of human-induced pluripotent stem cells (hiPSCs) into lineage-specific oligodendrocytes (OLs). However, effective strategies currently rely mainly on genome-integrating viruses. Here we show that a synthetic modified messenger RNA (smRNA)-based reprogramming method that leads to the generation of transgene-free OLs has been developed. An smRNA encoding a modified form of OLIG2, in which the serine 147 phosphorylation site is replaced with alanine, OLIG2^S147A, is designed to reprogram hiPSCs into OLs. We demonstrate that repeated administration of the smRNA encoding OLIG2^S147A lead to higher and more stable protein expression. Using the single-mutant OLIG2 smRNA morphogen, we establish a 6-day smRNA transfection protocol, and glial induction lead to rapid NG2⁺ OL progenitor cell (OPC) generation (>70% purity) from hiPSC. The smRNA-induced NG2⁺ OPCs can mature into functional OLs in vitro and promote remyelination in vivo. Taken together, we present a safe and efficient smRNA-driven strategy for hiPSC differentiation into OLs, which may be utilized for therapeutic OPC/OL transplantation in patients with neurodegenerative disease.