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Transitory structures known as ganglionic eminences (GEs) produce interneurons which undergo tangential migration to the developing neocortex and manifest a spectrum of molecular identities, electrophysiology and connectivity during early cerebral development. Indeed, cortical interneurons (CINs) were derived from contiguous, subtly-demarcated progenitor zones inside these GEs as confirmed through lineage tracing, while also revealed a certain tight linkage between birthdate and derived interneuron subtypes. Indeed, past research had not settled in how CIN heterogeneity could arise, either proposed to emerge from prescribed lineage identity by transcriptional patterning in their progenitors or to have retained plasticity until their ultimate cell fates are defined by spatiotemporal context-specific changes. It is hopeful that recent advances in single cell technologies performed to human pluripotent stem cells (hPSCs)-derived CIN models would aid in resolving these all-time mysteries. The current work reviews how these stem cell-derived CIN cultures or related organoid model resembling their key transitory progenitor origin, i.e., the medial ganglionic eminence (MGE), shall recapitulate the emergence of subclass diversity, maturation and migratory decisions along human neurogenesis. These organoids were adopted to reveal the subtle modifications in transcriptional landscapes in response to local connections, guidance cues or finetuning miRNA actions. Aspirations in the field seek to adopt the fusion of hPSC-derived cortical organoid with MGE-like organoid as the best approach to investigate defects which staged cerebral diseases for its expansive ability to faithfully model potential migratory or specification cues giving rise to disease phenotypes; further advocates a thorough understanding of the intricated, complex interactions brought about by CIN diversity at the genetic level.

Background & Aims The paradox of hepatic insulin resistance describes the inability for liver to respond to bioenergetics hormones in suppressing gluconeogenesis whilst maintaining lipid synthesis. Here, we report the deficiency of miR-192-3p in the livers of mice with diabetes and its role in alleviating hepatic steatosis. Methods As conventional pre-microRNA (miRNA) stem-loop overexpression only boosts guiding strand (i.e. miR-192-5p) expression, we adopted an artificial AAV(DJ)-directed, RNA Pol III promoter-driven miRNA hairpin construct for star-strand-specific overexpression in the liver. Liver steatosis and insulin resistance markers were evaluated in primary hepatocytes, mice with diabetes, and mice with excessive carbohydrate consumption. Results Functional loss of miR-192-3p in liver exacerbated hepatic micro-vesicular steatosis and insulin resistance in either mice with diabetes or wild-type mice with excessive fructose consumption. Liver-specific overexpression of miR-192-3p effectively halted hepatic steatosis and ameliorated insulin resistance in these mice models. Likewise, hepatocytes overexpressing miR-192-3p exhibited improved lipid accumulation, accompanied with decreases in lipogenesis and lipid-accumulation-related transcripts. Mechanistically, glucocorticoid receptor (GCR, also known as nuclear receptor subfamily 3, group C, member 1 [NR3C1]) was demonstrated to be negatively regulated by miR-192-3p. The effect of miR-192-3p on mitigating micro-vesicular steatosis was ablated by the reactivation of NR3C1. Conclusions The star strand miR-192-3p was an undermined glycerolipid regulator involved in controlling fat accumulation and insulin sensitivity in liver through blockade of hepatic GCR signalling; this miRNA may serve as a potential therapeutic option for the common co-mobility of diabetic mellitus and fatty liver disease. Lay summary The potential regulatory activity of star strand microRNA (miRNA) species has been substantially underestimated. In this study, we investigate the role and mechanism of an overlooked star strand miRNA (miR-192-3p) in regulating hepatic steatosis and insulin signalling in the livers of mice with diabetes and mice under excessive carbohydrate consumption., Graphical abstract, Highlights • Liver-specific knockdown of miR-192-3p recapitulated functional loss of the miRNA as in mice with diabetes. • This knockdown was characterised by pronounced hepatic micro-vesicular steatosis coupled to insulin resistance. • In vivo overexpression of miR-192-3p alleviated hepatic steatosis in mice with diabetes and wild-type mice with excessive fructose consumption. • Glucocorticoid receptor (also known as NR3C1) was discovered as the immediate target of miR-192-3p in regulating hepatic lipid turnover and storage.