1.Single-cell and Spatial Omics Technologies:Deciphering The Process of Animal Skeletal Muscle Development
Ming-Fu XIONG ; Si-Yuan KONG ; Yong-Sheng ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(11):1566-1578
As an important tissue of the body(accounting for approximately 40%of body weight),skel-etal muscle is composed of various cell types such as muscle fibers,muscle stem cells,and endothelial cells.It participates in physiological processes including movement,energy metabolism,and internal en-vironment homeostasis through temporal and spatial specific regulation.Its development is divided into two critical stages:embryonic and postnatal periods.Abnormal development can lead to diseases such as muscular dystrophy and directly affect the yield and quality of livestock meat.In recent years,the combi-nation of single-cell transcriptomics(scRNA-seq)and spatial omics(single-cell spatial omics technolo-gy)has provided a high-resolution research tool for analyzing the spatiotemporal dynamic regulatory net-work and intercellular interactions in skeletal muscle development.This article reviews the molecular mechanisms of skeletal muscle development and its application value in animal husbandry breeding,and systematically combs the research progress,analysis processes,data resources,and future directions of single-cell omics,spatial omics,and single-cell spatial omics technology in skeletal muscle development.Among them,single-cell omics can reveal the heterogeneity of skeletal muscle cells,myofiber differentia-tion trajectories in different livestock and poultry(such as cattle,pigs,and Tibetan chickens)through methods like pseudotime analysis and RNA velocity analysis.Furthermore,single-cell omics can identify key transcription factors(e.g.,MYF5,MYOD1)and cell communication pathways(e.g.,FGF7-FG-FR2),and simultaneously clarify the molecular differences in myoblast differentiation timing and cell composition ratio among different breeds.Relying on technologies such as Visium and Seq-Scope,spatial omics realizes the spatial localization of gene expression in pathological models of mice,Atlantic salmon,and broiler chickens.Spatial omics also clarifies the spatial distribution laws of neuromuscular junction region-specific genes and inflammation-fibrosis cascade reactions,and makes up for the defect of losing spatial context in single-cell technology.Although there are limited direct application cases of single-cell spatial omics technology,it has already analyzed the abnormal fate of myoblasts in facioscapulohumeral muscular dystrophy through MERFISH technology.In terms of technology selection,it is necessary to consider research objectives,molecular modalities,and resolution requirements.At the same time,data analysis needs to address challenges such as data sparsity through methods like DCA denoising and RCTD cell type mapping.In addition,this article summarizes 16 muscle development-related databases inclu-ding HCA and PanglaoDB.This review further discusses the potential applications of these three types of technologies in the directional regulation of myoblast fate,precise intervention in the growth cycle,im-provement of microenvironment interactions,and the development of multi-omics genetic breeding mod-els.This paper is providing a more comprehensive and detailed theoretical reference and technical sup-port for basic research on skeletal muscle development and practical applications in the animal husbandry industry.
2.Single-cell and Spatial Omics Technologies:Deciphering The Process of Animal Skeletal Muscle Development
Ming-Fu XIONG ; Si-Yuan KONG ; Yong-Sheng ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(11):1566-1578
As an important tissue of the body(accounting for approximately 40%of body weight),skel-etal muscle is composed of various cell types such as muscle fibers,muscle stem cells,and endothelial cells.It participates in physiological processes including movement,energy metabolism,and internal en-vironment homeostasis through temporal and spatial specific regulation.Its development is divided into two critical stages:embryonic and postnatal periods.Abnormal development can lead to diseases such as muscular dystrophy and directly affect the yield and quality of livestock meat.In recent years,the combi-nation of single-cell transcriptomics(scRNA-seq)and spatial omics(single-cell spatial omics technolo-gy)has provided a high-resolution research tool for analyzing the spatiotemporal dynamic regulatory net-work and intercellular interactions in skeletal muscle development.This article reviews the molecular mechanisms of skeletal muscle development and its application value in animal husbandry breeding,and systematically combs the research progress,analysis processes,data resources,and future directions of single-cell omics,spatial omics,and single-cell spatial omics technology in skeletal muscle development.Among them,single-cell omics can reveal the heterogeneity of skeletal muscle cells,myofiber differentia-tion trajectories in different livestock and poultry(such as cattle,pigs,and Tibetan chickens)through methods like pseudotime analysis and RNA velocity analysis.Furthermore,single-cell omics can identify key transcription factors(e.g.,MYF5,MYOD1)and cell communication pathways(e.g.,FGF7-FG-FR2),and simultaneously clarify the molecular differences in myoblast differentiation timing and cell composition ratio among different breeds.Relying on technologies such as Visium and Seq-Scope,spatial omics realizes the spatial localization of gene expression in pathological models of mice,Atlantic salmon,and broiler chickens.Spatial omics also clarifies the spatial distribution laws of neuromuscular junction region-specific genes and inflammation-fibrosis cascade reactions,and makes up for the defect of losing spatial context in single-cell technology.Although there are limited direct application cases of single-cell spatial omics technology,it has already analyzed the abnormal fate of myoblasts in facioscapulohumeral muscular dystrophy through MERFISH technology.In terms of technology selection,it is necessary to consider research objectives,molecular modalities,and resolution requirements.At the same time,data analysis needs to address challenges such as data sparsity through methods like DCA denoising and RCTD cell type mapping.In addition,this article summarizes 16 muscle development-related databases inclu-ding HCA and PanglaoDB.This review further discusses the potential applications of these three types of technologies in the directional regulation of myoblast fate,precise intervention in the growth cycle,im-provement of microenvironment interactions,and the development of multi-omics genetic breeding mod-els.This paper is providing a more comprehensive and detailed theoretical reference and technical sup-port for basic research on skeletal muscle development and practical applications in the animal husbandry industry.
3.Efficacy and Side Effects of Mixed-Strategy Electroconvulsive Therapy: A Proof-of-Concept Randomized Clinical Trial on Late Life Depression
Si-wen LV ; Yan SUN ; Yang CHEN ; Chen WANG ; Xin-hui XIE ; Xiao-min HU ; Hong HONG ; Lou-Feng ZHANG ; Nan-nan ZHU ; Peng-yv XIE ; Li ZHANG ; Ling CHEN ; Xiao-ming KONG
Psychiatry Investigation 2024;21(7):772-781
Objective:
Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects
Methods:
This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies.
Results:
In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004).
Conclusion
msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.
4.Clinical effect of Ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema
Kong-Qian HUANG ; Lu-Hong LIU ; Min LI ; Si-Ming ZENG ; Xue-Jin WU ; Hai-Bin ZHONG ; Li-Fei CHEN ; Xiao-Ling LAI
International Eye Science 2022;22(8):1377-1380
AIM:To observe the clinical effect of ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema(DME). METHODS:There were 52 eyes of 52 patients diagnosed with severe DME who admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from June 2016 to September 2019. The patients were randomly divided into the observation group(26 patients with 26 eyes, treated with ranibizumab combined with 577nm micropulse laser)and the control group(26 patients with 26 eyes, treated with ranibizumab alone). Patients in both groups received intravitreal injection of ranibizumab with “3+PRN” regimen. Followed up at 9mo after treatment to observe the central macular thickness(CMT), the best corrected visual acuity(BCVA)and the times of intravitreal injection of ranibizumab in the two groups.RESULTS:Compared with before treatment, the CMT and BCVA of the two groups were significantly improved at each time point after treatment(all P<0.001), but there was no difference between the two groups(P>0.05). During the follow-up period, the times of vitreous injection of ranibizumabin the observation group was significantly less than that in the control group(5.88±1.24 times vs 7.12±1.24 times, P=0.001). CONCLUSION:Both ranibizumab combined with 577nm micropulse laser and ranibizumab alone are effective in reducing edema and improving vision in patients with severe DME, but the combination therapy reduces the times of injection.
5. Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice
Si-Yuan PAN ; Xue-Lan SONG ; Zhao-Heng LIN ; Hai-Chuan TAI ; Si-Yuan PAN ; Qing YU ; Yi ZHANG ; Gan LUO ; Xiao-Yan WANG ; Nan SUN ; Zhu-Sheng CHU ; Yi ZHANG ; Pei-Li ZHU ; Zhi-Ling YU ; Kam-Ming KO
Asian Pacific Journal of Tropical Biomedicine 2022;12(2):59-68
Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).
6. The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction
Qian WANG ; Ying KONG ; Song LIN ; Ding-Yu WU ; Jian HU ; Lang HUANG ; Wen-Si ZANG ; Xiao-Wen LI ; Jian-Ming YANG ; Tian-Ming GAO
Neuroscience Bulletin 2021;37(9):1303-1313
Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca
7.The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction.
Qian WANG ; Ying KONG ; Song LIN ; Ding-Yu WU ; Jian HU ; Lang HUANG ; Wen-Si ZANG ; Xiao-Wen LI ; Jian-Ming YANG ; Tian-Ming GAO
Neuroscience Bulletin 2021;37(9):1303-1313
Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca
Adenosine Triphosphate
;
Animals
;
Antidepressive Agents/therapeutic use*
;
Caloric Restriction
;
Mice
;
Mice, Knockout
;
Prefrontal Cortex
8.A comparison between endoscopic CO2 laser cauterization and open neck surgery in the treatment of congenital piriform fistula.
Shu Ling HUANG ; Liang Si CHEN ; Mi Mi XU ; Xi Xiang GONG ; Bei ZHANG ; Lu LIANG ; Xiao Li SHENG ; Jian Dong ZHAN ; Xiao Ning LUO ; Zhong Ming LU ; Si Yi ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(6):619-625
Objective: To compare the efficacy, advantages and disadvantages of endoscopic CO2 laser cauterization (ECLC) and open neck surgery in the treatment of congenital pyriform sinus fistula (CPSF). Methods: From September 2014 to March 2017, 80 cases with confirmed diagnosis of CPSF received initial treatment at Guangdong Provincial People's Hospital were prospectively analyzed, including 34 males and 46 females, aged 18 to 672 (194.17±141.18) months. They were consecutively divided into endoscopic group and open-surgery group, with 40 cases in each group. Both groups of patients received surgical treatment under general anesthesia. The endoscopic group was treated by endoscopic CO2 laser cauterization, and the open-surgery group underwent the following surgery: first, we performed suspension laryngoscopy examination to confirm the presence of fistula in the bottom of the piriform fossa, then open-neck resection of congenital piriform sinus fistula with recurrent laryngeal nerve and/or lateral branch of superior laryngeal nerve anatomy plus partial thyroidectomy were performed. The data between the two groups were compared, including the operative time, intraoperative blood loss, postoperative pain, average length of stay, neck cosmetic scores, complications and cure rates. All patients were followed up in outpatient clinics. Statistical analysis was performed using SPSS 20.0 software. P<0.05 indicates that the difference is statistically significant. Results: All patients were successfully completed the operation. The operative time, intraoperative blood loss, postoperative pain and average length of hospital stay in the endoscopic group were significantly less than those in the open group [(27.4±5.5) min to (105.8±52.5) min, (0.6±0.5) ml to (33.6±41.5) ml, (1.7±0.9) points to (4.6±0.7) points, (5.9±2.9)d to(8.9±3.3)d, t values were-9.400, -5.031, -16.199, -4.293, P values were all<0.01]; The neck cosmetic score in the endoscopy group was significantly greater than that of the open group [(9.9±0.4) against (5.8±0.9) points, t=25.847, P<0.01]. Compared with the open group (15.0%, 6/40), the complication rate of the endoscopic group (7.5%, 3/40) was not statistically significant (χ²=0.50, P>0.05). Three months after the first treatment, the cure rate in the endoscopic group (82.5%, 33/40) was significantly lower than that in the open-neck group (100.0%, 40/40), χ²=5.64, P<0.05. The follow-up time was 12 months after the last treatment. Eighty cases were followed up and none was lost to follow-up. During the follow-up period, the cure rate of the endoscopy group (97.5%, 39/40) was compared with that of the open group (100.0%, 40/40), and the difference was not statistically significant. Conclusions: In the treatment of CPSF, the two-surgical method each has their advantages. Compared with open-neck surgery, ECLC is simpler, repeatable. ECLC has shorter time in operation and hospital stay, less complications, and less postoperative pain and more precise cosmetic results. It could be preferred for the initial treatment of CPSF and relapsed cases after cauterization. But subject to relatively low cure rate of one-time cauterization and uncertain long-term efficacy, it cannot completely replace the open-neck surgery at present.
Carbon Dioxide
;
Cautery
;
Endoscopy
;
Female
;
Fistula/surgery*
;
Humans
;
Lasers, Gas/therapeutic use*
;
Male
;
Pyriform Sinus/surgery*
;
Retrospective Studies
;
Treatment Outcome
9.Astrocytic GABA Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF.
Ji-Hong LIU ; Ze-Lin LI ; Yi-Si LIU ; Huai-De CHU ; Neng-Yuan HU ; Ding-Yu WU ; Lang HUANG ; Shu-Ji LI ; Xiao-Wen LI ; Jian-Ming YANG ; Tian-Ming GAO
Neuroscience Bulletin 2020;36(7):705-718
Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.
10.Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines.
Neng-Yuan HU ; Ya-Ting CHEN ; Qian WANG ; Wei JIE ; Yi-Si LIU ; Qiang-Long YOU ; Ze-Lin LI ; Xiao-Wen LI ; Sophie REIBEL ; Frank W PFRIEGER ; Jian-Ming YANG ; Tian-Ming GAO
Neuroscience Bulletin 2020;36(5):530-544
Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.

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