Functional hepatobiliary organoids recapitulate liver development and reveal essential drivers of hepatobiliary cell fate determination.

During liver development, hepatocytes, and cholangiocytes are concurrently differentiated from common liver progenitor cells and are assembled into hepatobiliary architecture to perform proper hepatic function. However, the generation of functional hepatobiliary architecture from hepatocytes is still challenging, and the exact molecular drivers of hepatobiliary cell lineage determination is largely unknown. In this study, functional hepatobiliary organoids (HBOs) are generated from hepatocytes.

Promotion of nonalcoholic steatohepatitis by RNA N-methyladenosine reader IGF2BP2 in mice.

Nonalcoholic steatohepatitis (NASH) has emerged as the major cause of end-stage liver diseases. However, an incomplete understanding of its molecular mechanisms severely dampens the development of pharmacotherapies. In the present study, through systematic screening of genome-wide mRNA expression from three mouse models of hepatic inflammation and fibrosis, we identified IGF2BP2, an N-methyladenosine modification reader, as a key regulator that promotes NASH progression in mice.

Restoring carboxypeptidase E rescues BDNF maturation and neurogenesis in aged brains.

Adult neurogenesis declines with age due to the less functional neural stem cells (NSCs) and niches, but the underlying molecular bases for this impaired condition remain unclear. Here we analyzed >55,000 single-cell transcriptomes from two discrete neurogenic niches across the mouse lifespan, and identified new features and populations in NSCs, new markers, and neurogenic regional-specific alternations during aging. Intercellular communication analysis revealed defects in brain-derived neurotrophic factor (BDNF)-TrkB signaling cascade in old NSCs.

A multi-omic landscape of steatosis-to-NASH progression.

Nonalcoholic steatohepatitis (NASH) has emerged as a major cause of liver failure and hepatocellular carcinoma. Investigation into the molecular mechanisms that underlie steatosis-to-NASH progression is key to understanding the development of NASH pathophysiology. Here, we present comprehensive multi-omic profiles of preclinical animal models to identify genes, non-coding RNAs, proteins, and plasma metabolites involved in this progression.