Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.

Conjugated Polyelectrolyte Containing a High Density of Pendant Phenylboronic Acid Groups for Dopamine Detection.

A fluorescent sensing system based on a conjugated polyelectrolyte was constructed to detect dopamine (DA) in complex samples. The conjugated polymer PFPE-PBA with poly[fluorenyl-alt-p-phenyleneethynylene] (PFPE) as the backbone and carrying four pendant phenylboronic acid (PBA) groups in each repeat unit was synthesized. PFPE-PBA was found to have good solubility in polar solvents. After optimization, glycine-NaOH at pH 10 was selected as the buffer, and the solvent composition of the system was set to methanol/water (9/1 by volume). Titration experiments showed that DA could effectively quench the fluorescence of the polymer solution with a response time within 60 s and a limit of detection of 23 nM. Polyols, cations, and other possible interfering substances do not significantly affect the fluorescence of the polymer, thereby allowing for the highly selective detection of DA. Furthermore, quantitative determination of DA in spiked serum and artificial urine samples was successfully demonstrated, with recoveries ranging from 96.7 to 104%. Preliminary mechanism studies suggest that the pedant PBAs capture DA via reaction with the catechol group, and the fluorescence quenching is most likely due to the photoinduced electron transfer between the aromatic part of DA and the conjugated backbone. This study provides a general strategy for the future design of conjugated polyelectrolyte-based sensing systems.

Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength.

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)-induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX-induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX-induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM- and Akk-induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX-induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM-induced anti-osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone.