Rationale: Reconstruction of hair follicles (HFs) and eccrine sweat glands (ESGs) is essential for functional skin regeneration. In skin reconstruction research, we found that foreskin-derived epidermal cells reconstructed HF organoids unidirectionally, but not ESG organoids. Methods: To investigate key genes and pathways influencing the fate of ESG and HF, a transcriptome profiling of ESG placode-containing skin and HF placode-containing skin was employed, and key DEGs were identified and validated by RT-qPCR and immunofluorescence staining in mice and rats. Subsequently, adult human epidermal cell-derived organoids were reconstructed to probe functional roles and mechanisms of FGF7 and FGF10 by series of approaches integrating RT-qPCR, immunofluorescence-staining, WB, apoptosis assay, and pathway interference assay. Results: All members of FGF7 subfamily were among the key DEGs screened, the differential expression of FGF7 and FGF10 and their receptors FGFR1/FGFR2 was verified between ESG placode-containing skin and HF placode-containing skin. In vivo and in vitro Matrigel plug models showed that both FGF7 and FGF10 promoted fate transition of human epidermal cell-derived organoids to ESG phenotype organoids, FGF7 and FGF10 had a synergistic effect, and mainly function through the FGFR1/2-MEK1/2-ERK1/2 pathway. Conclusions: Adult epidermal cells can be manipulated to reconstruct personalized HF and ESG to meet different needs.

The lung airways exhibit distinct features with long, wide proximal branches and short, thin distal branches, crucial for optimal respiratory function. In this study, we investigated the mechanism behind this hierarchical structure through experiments and modeling, focusing on the regulation of branch length and width during the pseudoglandular stage. To evaluate the response of mouse lung epithelium to fibroblast growth factor 10 (FGF10), we monitored the activity of extracellular signal-regulated kinase (ERK). ERK activity exhibited an increase dependent on the curvature of the epithelial tissue, which gradually decreased with the progression of development. We then constructed a computational model that incorporates curvature-dependent growth to predict its impact on branch formation. It was demonstrated that branch length is determined by the curvature dependence of growth. Next, in exploring branch width regulation, we considered the effect of apical constriction, a mechanism we had previously proposed to be regulated by Wnt signaling. Analysis of a mathematical model representing apical constriction showed that branch width is determined by cell shape. Finally, we constructed an integrated computational model that includes curvature-dependent growth and cell shape controls, confirming their coordination in regulating branch formation. This study proposed that changes in the autonomous property of the epithelium may be responsible for the progressive branch morphology.

Branching morphogenesis is a characteristic feature of many essential organs, such as the lung and kidney, and most glands, and is the net result of two tissue behaviors: branch point initiation and elongation. Each branched organ has a distinct architecture customized to its physiological function, but how patterning occurs in these ramified tubular structures is a fundamental problem of development. Here, we use quantitative 3D morphometrics, time-lapse imaging, manipulation of ex vivo cultured mouse embryonic organs and mice deficient in the planar cell polarity component Vangl2 to address this question in the developing mammary gland. Our results show that the embryonic epithelial trees are highly complex in topology owing to the flexible use of two distinct modes of branch point initiation: lateral branching and tip bifurcation. This non-stereotypy was contrasted by the remarkably constant average branch frequency, indicating a ductal growth invariant, yet stochastic, propensity to branch. The probability of branching was malleable and could be tuned by manipulating the Fgf10 and Tgfβ1 pathways. Finally, our in vivo data and ex vivo time-lapse imaging suggest the involvement of tissue rearrangements in mammary branch elongation.

BACKGROUND: The cause of duodenal atresia (DA) is not known. Tandler\'s \"solid cord\" hypothesis conflicts with current biological evidence. In humans, a genetic aetiology is supported by the association with Trisomy 21. Interruption of Fgf10 is the strongest genetic link to DA in mice, demonstrating an increased incidence and severity as embryos mature. This project aimed to develop an organoid model to facilitate ex vivo DA research on the FGF10/FGFR2b signalling pathway. We hypothesised that DA morphology represents an evolving spectrum of disease and that Fgf10 knockout organoids would vary in growth pattern compared to wild-type.
METHODS: Organoids were cultured from the duodenum of E12.5 Fgf10 knockout, heterozygous and wild-type embryos, using an air-liquid interface with Growth Factor reduced Matrigel. Organoids were photographed every 48 h to observe growth. Organoids were isolated and fixed after 14 days, then stained with DAPI, KI-67, and cytokeratin to demonstrate proliferation and differentiation.
RESULTS: Wild-type duodenum developed into crypt-forming organoids. Fgf10 heterozygous duodenum failed to progress beyond the development stage of spheroids. Fgf10 knockout duodenum failed to demonstrate any growth. Wholemount staining showed the greatest cell proliferation and differentiation in wild-type tissue.
CONCLUSIONS: This research presents a novel concept for the growth of embryonic gastrointestinal tissue to inform normal biology. The small sample numbers and restricted culture duration limit longer-term growth analysis. While this model serves as a potential ex vivo setting for future research, that research should consider organoid models with greater standardisation and other gastrointestinal regions.
METHODS: Animal/laboratory study.

How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers for early fate specification has prevented the delineation of the features and spatial localization of MaSC-derived lineage-committed progenitors. Here, using single-cell RNA sequencing from E13.5 to birth, we produced an atlas of matched mouse mammary epithelium and mesenchyme and reconstructed the differentiation trajectories of MaSCs toward basal and luminal fate. We show that murine MaSCs exhibit lineage commitment just prior to the first sprouting events of mammary branching morphogenesis at E15.5. We identify early molecular markers for committed and multipotent MaSCs and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially restricted cell populations, and that dermal mesenchyme-produced FGF10 is essential for embryonic mammary branching morphogenesis. Altogether, our data elucidate the spatiotemporal signals underlying lineage specification of multipotent MaSCs, and uncover the signals from mesenchymal cells that guide mammary branching morphogenesis.

Particulate matter (PM) is considered the fundamental component of atmospheric pollutants and is associated with the pathogenesis of many respiratory diseases. Fibroblast growth factor 10 (FGF10) mediates mesenchymal-epithelial signaling and has been linked with the repair process of PM-induced lung injury (PMLI). However, the pathogenic mechanism of PMLI and the specific FGF10 protective mechanism against this injury are still undetermined. PM was administered in vivo into murine airways or in vitro to human bronchial epithelial cells (HBECs), and the inflammatory response and ferroptosis-related proteins SLC7A11 and GPX4 were assessed. The present research investigates the FGF10-mediated regulation of ferroptosis in PMLI mice models in vivo and HBECs in vitro. The results showed that FGF10 pretreatment reduced PM-mediated oxidative damage and ferroptosis in vivo and in vitro. Furthermore, FGF10 pretreatment led to reduced oxidative stress, decreased secretion of inflammatory mediators, and activation of the Nrf2-dependent antioxidant signaling. Additionally, silencing of Nrf2 using siRNA in the context of FGF10 treatment attenuated the effect on ferroptosis. Altogether, both in vivo and in vitro assessments confirmed that FGF10 protects against PMLI by inhibiting ferroptosis via the Nrf2 signaling. Thus, FGF10 can be used as a novel ferroptosis suppressor and a potential treatment target in PMLI.

Fibroblast growth factor 10 (FGF10) plays critical roles in oocyte maturation and embryonic development; however, the specific pathway by which FGF10 promotes in vitro maturation of buffalo oocytes remains elusive. The present study was aimed at investigating the mechanism underlying effects of the FGF10-mediated extracellular regulated protein kinases (ERK) pathway on oocyte maturation and embryonic development in vitro. MEK1/2 (mitogen-activated protein kinase kinase) inhibitor U0126, alone or in combination with FGF10, was added to the maturation culture medium during maturation of the cumulus oocyte complex. Morphological observations, orcein staining, apoptosis detection, and quantitative real-time PCR were performed to evaluate oocyte maturation, embryonic development, and gene expression. U0126 affected oocyte maturation and embryonic development in vitro by substantially reducing the nuclear maturation of oocytes and expansion of the cumulus while increasing the apoptosis of cumulus cells. However, it did not have a considerable effect on glucose metabolism. These findings suggest that blocking the MEK/ERK pathway is detrimental to the maturation and embryonic development potential of buffalo oocytes. Overall, FGF10 may regulate the nuclear maturation of oocytes and cumulus cell expansion and apoptosis but not glucose metabolism through the MEK/ERK pathway. Our findings indicate that FGF10 regulates resumption of meiosis and expansion and survival of cumulus cells via MEK/ERK signaling during in vitro maturation of buffalo cumulus oocyte complexes. Elucidation of the mechanism of action of FGF10 and insights into oocyte maturation should advance buffalo breeding. Further studies should examine whether enhancement of MEK/ERK signaling improves embryonic development in buffalo.

In amniote limbs, Fibroblast Growth Factor 10 (FGF10) is essential for limb development, but whether this function is broadly conserved in tetrapods and/or involved in adult limb regeneration remains unknown. To tackle this question, we established Fgf10 mutant lines in the newt Pleurodeles waltl which has amazing regenerative ability. While Fgf10 mutant forelimbs develop normally, the hindlimbs fail to develop and downregulate FGF target genes. Despite these developmental defects, Fgf10 mutants were able to regenerate normal hindlimbs rather than recapitulating the embryonic phenotype. Together, our results demonstrate an important role for FGF10 in hindlimb formation, but little or no function in regeneration, suggesting that different mechanisms operate during limb regeneration versus development.

Vertebrate limbs start to develop as paired protrusions from the lateral plate mesoderm at specific locations of the body with forelimb buds developing anteriorly and hindlimb buds posteriorly. During the initiation process, limb progenitor cells maintain active proliferation to form protrusions and start to express Fgf10, which triggers molecular processes for outgrowth and patterning. Although both processes occur in both types of limbs, forelimbs (Tbx5), and hindlimbs (Isl1) utilize distinct transcriptional systems to trigger their development. Here, we report that Sall1 and Sall4, zinc finger transcription factor genes, regulate hindlimb initiation in mouse embryos. Compared to the 100% frequency loss of hindlimb buds in TCre; Isl1 conditional knockouts, Hoxb6Cre; Isl1 conditional knockout causes a hypomorphic phenotype with only approximately 5% of mutants lacking the hindlimb. Our previous study of SALL4 ChIP-seq showed SALL4 enrichment in an Isl1 enhancer, suggesting that SALL4 acts upstream of Isl1. Removing 1 allele of Sall4 from the hypomorphic Hoxb6Cre; Isl1 mutant background caused loss of hindlimbs, but removing both alleles caused an even higher frequency of loss of hindlimbs, suggesting a genetic interaction between Sall4 and Isl1. Furthermore, TCre-mediated conditional double knockouts of Sall1 and Sall4 displayed a loss of expression of hindlimb progenitor markers (Isl1, Pitx1, Tbx4) and failed to develop hindlimbs, demonstrating functional redundancy between Sall1 and Sall4. Our data provides genetic evidence that Sall1 and Sall4 act as master regulators of hindlimb initiation.

This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science, SCOPUS and Cochrane Central were searched to obtain studies about blood derivatives on wound healing until October 2023. R 4.2.0 and Stata 15.0 softwares were used for data analysis. Forty-four studies comprising 5164 patients were included. The results of network meta-analysis showed that the healing area from high to low was GF + ORCCB, ORCCB, GF, PRF, Unnas paste dressing, APG, PRP injection, PRP, PRP + thrombin gel, PPP, HPL, CT. The healing time from low to high was PRP + thrombin gel, GF, PRP, PC + K, PC, APG, PRF, CT, Silver sulfadiazine ointment. The number of patients cured from high to low was APG, PRP injection, PRP, Aurix, PRF, Leucopatch, HPL, Antimicrobial Ointment Dressing, CT, 60 μg/cm2 repifermin, 120 μg/cm2 repifermin, AFG, PPP. The order of analgesic effect from high to low was AFG, Aminogam gel, PRF, PRP, Oxidised oil, APG, GF, CT. The order of the number of wound infection cases from low to high is APG, 20 μg/cm2 repifermin, 60 μg/cm2 repifermin, PRP, LeucoPatch, CT, PPP, Antiseptic ointment dressing. Healing area: GF + ORCCB had the best effect; Healing time: PRP + thrombin gel took the shortest time. The number of cured patients and the reduction of wound infection: APG has the best effect. Analgesic effect: AFG has the best effect. More studies with large sample sizes are needed to confirm the above findings.