The classical model of tissue renewal posits that small numbers of quiescent stem cells (SCs) give rise to proliferating transit-amplifying cells before terminal differentiation. However, many organs house pools of SCs with proliferative and differentiation potentials that diverge from this template. Resolving SC identity and organization is therefore central to understanding tissue renewal. Here, using a combination of single-cell RNA sequencing (scRNA-seq), mouse genetics and tissue injury approaches, we uncover cellular hierarchies and mechanisms that underlie the maintenance and repair of the continuously growing mouse incisor. Our results reveal that, during homeostasis, a group of actively cycling epithelial progenitors generates enamel-producing ameloblasts and adjacent layers of non-ameloblast cells. After injury, tissue repair was achieved through transient increases in progenitor-cell proliferation and through direct conversion of Notch1-expressing cells to ameloblasts. We elucidate epithelial SC identity, position and function, providing a mechanistic basis for the homeostasis and repair of a fast-turnover ectodermal appendage.

Extracellular vesicles (EVs), or exosomes, are nanovesicles of endocytic origin that carry host and pathogen-derived protein, nucleic acid, and lipid cargos. They are secreted by most cell types and play important roles in normal cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses and pathophysiological processes. New research is beginning to decipher how EVs influence viral and bacterial pathogenesis. In this review, we will describe how EVs influence viral and bacterial pathogenesis by spreading pathogen-derived factors and how they can promote and inhibit the immune response to these pathogens. We will also discuss the emerging potential of EVs as diagnostic and therapeutic tools.

Mitochondrial dysfunction is a key feature of injury to numerous tissues and stem cell aging. Although the tissue regenerative role of mesenchymal stem cell (MSC)derived extracellular vesicles (MSC-EVs) is well known, their specific role in regulating mitochondrial function in target cells remains elusive. Here, we report that MSC-EVs attenuated mtDNA damage and inflammation after acute kidney injury (AKI) and that this effect was at least partially dependent on the mitochondrial transcription factor A (TFAM) pathway. In detail, TFAM and mtDNA were depleted by oxidative stress in MSCs from aged or diabetic donors. Higher levels of TFAM mRNA and mtDNA were detected in normal control (NC) MSC-EVs than in TFAM-knockdown (TFAM-KD) and aged EVs. EV-mediated TFAM mRNA transfer in recipient cells was unaffected by transcriptional inhibition. Accordingly, the application of MSC-EVs restored TFAM protein and TFAM-mtDNA complex (nucleoid) stability, thereby reversing mtDNA deletion and mitochondrial oxidative phosphorylation (OXPHOS) defects in injured renal tubular cells. Loss of TFAM also led to downregulation of multiple anti-inflammatory miRNAs and proteins in MSC-EVs. In vivo, intravenously injected EVs primarily accumulated in the liver, kidney, spleen, and lung. MSC-EVs attenuated renal lesion formation, mitochondrial damage, and inflammation in mice with AKI, whereas EVs from TFAM-KD or aged MSCs resulted in poor therapeutic outcomes. Moreover, TFAM overexpression (TFAM-OE) improved the rescue effect of MSC-EVs on mitochondrial damage and inflammation to some extent. This study suggests that MSC-EVs are promising nanotherapeutics for diseases characterized by mitochondrial damage, and TFAM signaling is essential for maintaining their regenerative capacity.

A I M : To i n v e s t i g a t e t h e e f f e c t o f a d m i s s i o n hypertriglyceridemia (HTG) on the episodes of severe acute pancreatitis (SAP). METHODS:One hundred and seventy-six patients with SAP were divided into HTG group (n = 45) and control group (n = 131) according to admission triglyceride (TG) ≥ 5.65 mmol/L and < 5.65 mmol/L, respectively. Demographics, etiology, underlying diseases, biochemical parameters, Ranson' s score, acute physiology and chronic heath evaluation Ⅱ (APACHE Ⅱ) score, Balthazar's computed tomography ( C T ) s c o r e , c o m p l i c a t i o n s a n d m o r t a l i ty w e r e compared. Correlation between admission TG and 24-h APACHE Ⅱ score was analyzed. RESULTS: SAP patients with HTG were younger (40.8 ± 9.3 years vs 52.6 ± 13.4 years, P < 0.05) with higher etiology rate of overeating, high-fat diet (40.0% vs 14.5%, P < 0.05) and alcohol abuse (46.7% vs 23.7%, P < 0.01), incidence rate of hypocalcemia (86.7% vs 63.4%, P < 0.01) and hypoalbuminemia (84.4% vs 60.3%, P < 0.01), 24-h APACHE Ⅱ score (13.6 ± 5.7 vs 10.7 ± 4.6, P < 0.01) and admission serum glucose (17.7 ± 7.7 vs 13.4 ± 6.1, P < 0.01), complication rate of renal failure (51.1% vs 16.8%, P < 0.01), shock (37.9% vs 14.5%, P < 0.01) and infection (37.4% vs 18.3%, P < 0.01) and mortality (13.1% vs 9.1%, P < 0.01). Logistic regression analysis showed a positive correlation between admission TG and 24-h APACHE Ⅱ score (r = 0 .509, P = 0.004).