GEO Dataset Transcriptomics Analysis for Early Gestational Fetal Scarless Healing Pattern of Mice

doi:10.19586/j.2095-2341.2022.0083

Current Biotechnology ›› 2023, Vol. 13 ›› Issue (1): 131-139.DOI: 10.19586/j.2095-2341.2022.0083

• Articles • Previous Articles Next Articles

GEO Dataset Transcriptomics Analysis for Early Gestational Fetal Scarless Healing Pattern of Mice

Zhen WANG¹^,²^,³(), Mawulikplimi Adzavon YAO¹^,²^,³(), Zijia LIU¹^,²^,³, Mengyu LIU¹^,²^,³, Fei XIE¹^,²^,³, Xuemei MA¹^,²^,³, Pengxiang ZHAO¹^,²^,³()

^1.Faculty of Environment and Life，Beijing University of Technology，Beijing 100124，China
^2.Beijing Molecular Hydrogen Research Center，Beijing 100124，China
^3.Beijing International Science and Technology，Cooperation Base of Antivirus Drug，Beijing 100124，China

Received:2022-05-19 Accepted:2022-06-30 Online:2023-01-25 Published:2023-02-07
Contact: Pengxiang ZHAO

胎儿早期小鼠无疤痕愈合的数据转录组学分析

王振¹^,²^,³(), YAO Mawulikplimi Adzavon¹^,²^,³(), 刘梓嘉¹^,²^,³, 刘梦昱¹^,²^,³, 谢飞¹^,²^,³, 马雪梅¹^,²^,³, 赵鹏翔¹^,²^,³()

^1.北京工业大学环境与生命学部，北京 100124
^2.北京氢分子研究中心，北京 100124
^3.抗病毒药物北京市国际科技合作基地，北京 100124

通讯作者: 赵鹏翔
作者简介:王振 E-mail：15128475758@163.com
Yao Mawulikplimi Adzavon E-mail：yaoadzavon@yahoo.fr；第一联系人：（王振、Yao Mawulikplimi Adzavon并列第一作者）
基金资助:
国家自然科学基金项目(81602408);军事后勤重点开放研究项目(BHJ17L018)

Abstract

Abstract:

Fetal skin heals scarlessly before a certain gestational age. For murine fetus， the cutoff gestational age of scarless healing is usually 14 days. Understanding and taking advantage of fetal scarless healing is critical for skin wound care and therapeutic trauma medicine development. Transcriptome analysis of different stages of fetal skin tissue should be one of the best ways towards such goals. Starting with the public Gene Expression Omnibus （GEO） microarray dataset GSE71619， which includes skin samples of mouse fetuses at day 14 of embryonic development （E14）， day 18 of embryonic development （E18）， and adult mice （W6）， the differential expressed genes （DEGs） were screened from the E14 （normally scarless skin） and （E18+W6）（normally scaring skin）. We obtained 4 654 DEGs （|log FC | ≥ 1， P<0.05） between each group. Venn diagram analysis and functional annotation of gene subsets identified 228 candidate genes with 4 distinct expression profiles across all groups. The genes involved in Cluster 3 were further analyzed. For the E14 group， up-regulated genes were mainly related to tissue remodeling， and extracellular matrix （ECM） composition functions， which promote wound healing. With protein-protein interaction， we identified 17 hub genes mainly belonging to the collagen family and fibrocytes migration-related genes. Therefore， we revealed for the first time the importance of ECM organization and fibrocytes activation in the scarless healing pattern of early gestational fetal. Essential genes promising in further research and application were also provided. The results provided fundamental knowledge for scarless wound care and cosmetic medicine industry.

Key words: scarless healing pattern, GEO dataset analysis, gestational fetus, gene enrichment

摘要：

已有研究显示，胎龄小于14 d的小鼠胎儿皮肤能够实现无疤痕创伤愈合。深入研究胎儿无疤痕愈合的分子机理，对于伤口护理方法优化与创伤医学的发展至关重要。利用已有数据库进行不同胎龄的小鼠皮肤组织转录组深入挖掘是常用的研究方法之一。从基因表达综合数据库（gene expression omnibus，GEO）在线数据库中寻找适合无疤痕愈合研究的基因表达谱芯片（GSE71619），其中包含胎龄14 d（E14）、胎龄18 d（E18）和6周龄成年鼠（W6）的皮肤组织样本。分别将无疤痕愈合（E14）与疤痕愈合皮肤组（E18+W6）对比分析，筛选差异表达基因（differential genes，DEGs），获得了4 654个DEGs（|log2 FC|≥1，P<0.05）。通过维恩图分析和基因功能注释确定了228个候选基因，并分为4个不同的Cluster。进一步重点分析了Cluster 3中涉及的基因：对于E14组，上调基因主要与促进伤口愈合的组织重塑和细胞外基质（extracellular matrix，ECM）形成功能相关。通过蛋白互作网络分析，确定了17个属于胶原家族和成纤维细胞迁移相关基因的关键基因。研究结果揭示了ECM的重塑和成纤维细胞活化在早期妊娠胎儿无疤痕愈合模式中的重要性，并筛选出可能的关键基因，为无疤痕伤口护理和创伤、医美领域提供了重要实验依据。

关键词: 无疤痕愈合, GEO数据集分析, 妊娠胎儿, 基因富集

CLC Number:

Q754

Zhen WANG, Mawulikplimi Adzavon YAO, Zijia LIU, Mengyu LIU, Fei XIE, Xuemei MA, Pengxiang ZHAO. GEO Dataset Transcriptomics Analysis for Early Gestational Fetal Scarless Healing Pattern of Mice[J]. Current Biotechnology, 2023, 13(1): 131-139.

王振, YAO Mawulikplimi Adzavon, 刘梓嘉, 刘梦昱, 谢飞, 马雪梅, 赵鹏翔. 胎儿早期小鼠无疤痕愈合的数据转录组学分析[J]. 生物技术进展, 2023, 13(1): 131-139.

Figures/Tables 6

References 23

1	WILLYARD C. Unlocking the secrets of scar-free skin healing[J]. Nature, 2018, 563(7732): 86-88.
2	HU M S, BORRELLI M R, JANUSZYK M, et al.. Pathway analysis of gene expression of E14 versus E18 fetal fibroblasts[J]. Adv. Wound Care (New Rochelle), 2018, 7(1): 1-10.
3	KEANE T J, HOREJS C M, STEVENS M M. Scarring vs. functional healing: matrix-based strategies to regulate tissue repair[J]. Adv. Drug Deliv. Rev., 2018, 129: 407-419.
4	郭博远, 郭大志, 刘诗博, 等. 早期介入高压氧提高寒冷应激下小鼠存活率并促进创面愈合的研究[J].生物技术进展,2020, 10(5): 534-540.
5	AMICONE L, MARCHETTI A, CICCHINI C J C. Exosome-associated circRNAs as key regulators of EMT in cancer[J/OL]. Cells, 2022, 11(10): 1716 [2022-05-06]. .
6	ZHANG J, ZHENG Y, LEE J, et al.. A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing[J/OL]. Nat. Commun., 2021, 12(1): 1670[2021-12-06]. .
7	HARRISON M R, ADZICK N S, LONGAKER M T, et al.. Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax[J]. N. Engl. J. Med., 1990, 322(22): 1582-1584.
8	GÜNES A, KIYAK H, YÜKSEL S, et al.. Predicting previable preterm premature rupture of membranes (pPPROM) before 24 weeks: maternal and fetal/neonatal risk factors for survival[J]. J. Obstet. Gynaecol., 2022, 42(4): 597-606.
9	ZHU Y, CAI Y, ZHENG B, et al.. Alteration of LncRNA expression in mice placentae after frozen embryo transfer is associated with increased fetal weight[J/OL]. Reproductive Bio., 2022, 22(2): 100646[2022-05-06]. .
10	NEGM W A, EL-KADEM A H, ELEKHNAWY E, et al.. Wound-healing potential of rhoifolin-rich fraction isolated from sanguisorba officinalis roots supported by enhancing re-epithelization, angiogenesis, anti-inflammatory, and antimicrobial effects[J/OL]. Pharmaceuticals (Basel), 2022, 15(2): 178[2022-06-10]. .
11	KUR-PIOTROWSKA A, KOPCEWICZ M, KOZAK L P, et al.. Neotenic phenomenon in gene expression in the skin of Foxn1- deficient (nude) mice-a projection for regenerative skin wound healing[J/OL]. BMC Geno., 2017, 18(1): 56[2021-05-06]. .
12	BULLARD J H, PURDOM E, HANSEN K D, et al.. Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments[J/OL]. BMC Bioinform., 2010, 11: 94[2021-04-06]. .
13	SWIFT D, CRESSWELL K, JOHNSON R, et al.. A review of normalization and differential abundance methods for microbiome counts data[J/OL].Wires. Comput. Sata., 2022: e1586[2022-04-06]. .
14	刘尚辉, 韦权峰, 雍嘉欣. 基于TCGA和GEO数据库的胃癌lncRNA筛选与ceRNA网络构建[J].生物技术进展,2022, 12(1): 149-157.
15	韩明盛, 胡鑫, 麻慧慈,等. 三阴性乳腺癌相关miRNA筛选及其靶基因的生物信息学分析[J].生物技术进展, 2022, 12(2): 296-304.
16	ZHOU Y, ZHOU B, PACHE L, et al.. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J/OL]. Nat. Commun., 2019, 10(1): 1523[2021-04-06]. .
17	DOWNS C A. Analysis of RAGE proteome and interactome in lung adenocarcinoma using PANTHER and STRING databases[J]. Bio. Res. Nurs., 2021, 23(4): 698-707.
18	UDDIN M P, MAMUN M A, AFJAL M I, et al.. Information-theoretic feature selection with segmentation-based folded principal component analysis (PCA) for hyperspectral image classification[J]. Inter. J. Remote Sens., 2021, 42(1): 286-321.
19	KATHJU S, SATISH L, RABIK C, et al.. Identification of differentially expressed genes in scarless wound healing utilizing polymerase chain reaction‐suppression subtractive hybridization[J]. Wound Repair Regen., 2006, 14(4): 413-420.
20	BRAZILE B L, BUTLER J R, PATNAIK S S, et al.. Biomechanical properties of acellular scar ECM during the acute to chronic stages of myocardial infarction[J/OL]. J. Mechan. Behav. Biomed. Mater., 2021, 116: 104342[2021-11-06]. .
21	DASEKE Ⅱ M J, CHALISE U, BECIROVIC-AGIC M, et al.. Neutrophil signaling during myocardial infarction wound repair[J/OL]. Cell. Signal., 2021, 77: 109816[2022-06-06]. .
22	PENG Y, HE D, GE X, et al.. Construction of heparin-based hydrogel incorporated with Cu5. 4O ultrasmall nanozymes for wound healing and inflammation inhibition[J]. Biol. Mater., 2021, 6(10): 3109-3124.
23	ZHAO S, GUAN B, MI Y, et al.. LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit[J]. Nat. Commun., 2021, 40(28): 4709-4724.

E14 vs E18		E14 vs W6
ID	功能描述	ID	功能描述
GO:0009888	组织发育	GO:0001501	骨骼系统发育
GO:0022610	生物黏附	GO:0009888	组织发育
GO:0002682	免疫系统的调控	GO:0072359	循环系统发育
GO:0007155	细胞黏附	GO:0009790	胚胎发育
GO:0060429	上皮组织的发育	GO:1903047	细胞有丝分裂周期过程
GO:0048646	形态发生中的解剖结构形成	GO:0048598	胚胎形态发生
GO:0072359	循环系统发育	GO:0008284	细胞增殖的正向调控
GO:0097435	超分子组织	GO:0035295	腔隙的形成发育
GO:0030855	上皮细胞分化	GO:0048646	形态发生中的解剖结构形成
GO:0009611	对创伤的反应	GO:0051241	多细胞生物过程的负调控
GO:0042060	创伤愈合	GO:0000278	细胞有丝分裂周期过程
GO:0003012	肌肉系统过程	GO:0035239	腔隙形态发生
GO:0008544	表皮发育	GO:0042127	细胞增殖调控
GO:0043588	皮肤发育	GO:0072358	心血管系统发育
GO:0009913	表皮细胞分化	GO:0051240	多细胞生物过程的正调控
GO:0030216	角化细胞分化	GO:0010564	细胞周期的调节
GO:0018149	肽交联	GO:0022402	细胞周期过程
GO:0032101	对外界刺激反应的调节	GO:0001944	维管系统发育
GO:0006954	炎症反应	GO:0001568	血管发育
GO:0061061	肌肉结构的发育	GO:0008283	细胞增殖

E14 vs E18		E14 vs W6
ID	功能描述	ID	功能描述
GO:0009888	组织发育	GO:0001501	骨骼系统发育
GO:0022610	生物黏附	GO:0009888	组织发育
GO:0002682	免疫系统的调控	GO:0072359	循环系统发育
GO:0007155	细胞黏附	GO:0009790	胚胎发育
GO:0060429	上皮组织的发育	GO:1903047	细胞有丝分裂周期过程
GO:0048646	形态发生中的解剖结构形成	GO:0048598	胚胎形态发生
GO:0072359	循环系统发育	GO:0008284	细胞增殖的正向调控
GO:0097435	超分子组织	GO:0035295	腔隙的形成发育
GO:0030855	上皮细胞分化	GO:0048646	形态发生中的解剖结构形成
GO:0009611	对创伤的反应	GO:0051241	多细胞生物过程的负调控
GO:0042060	创伤愈合	GO:0000278	细胞有丝分裂周期过程
GO:0003012	肌肉系统过程	GO:0035239	腔隙形态发生
GO:0008544	表皮发育	GO:0042127	细胞增殖调控
GO:0043588	皮肤发育	GO:0072358	心血管系统发育
GO:0009913	表皮细胞分化	GO:0051240	多细胞生物过程的正调控
GO:0030216	角化细胞分化	GO:0010564	细胞周期的调节
GO:0018149	肽交联	GO:0022402	细胞周期过程
GO:0032101	对外界刺激反应的调节	GO:0001944	维管系统发育
GO:0006954	炎症反应	GO:0001568	血管发育
GO:0061061	肌肉结构的发育	GO:0008283	细胞增殖

E14 vs E18		E14 vs W6
ID	功能描述	ID	功能描述
GO:0009891	生物合成过程的正向调控	GO:0044281	小分子代谢过程
GO:0051649	细胞内定域化建立	mmu01100	代谢途径
GO:0045595	细胞分化调控	GO:0006629	脂质代谢过程
GO:0033554	对压力的细胞应激	GO:0055114	氧化还原过程
GO:0022008	神经发生	GO:0006082	有机酸新陈代谢
GO:0048699	神经元产生	GO:0043436	酮酸代谢
GO:0030030	细胞投影组织	GO:0044255	细胞内脂质代谢
GO:0120036	质膜界细胞投影组织	GO:0019752	羧酸代谢过程
GO:0030182	神经元分化	GO:0032787	一元羧酸代谢过程
GO:0048666	神经元发育	GO:0051186	辅因子代谢
GO:0009790	胚胎发育	GO:0006631	脂肪酸代谢过程
GO:0060284	调控细胞发育	GO:0016042	脂肪分解
GO:0031175	神经元投影发育	GO:0016054	有机酸分解过程
GO:0051960	神经系统发育调节	GO:0046395	羧酸分解过程
GO:0007417	中枢神经系统发育	GO:0044242	细胞脂质降解
GO:0050767	神经形成调控	mmu03320	PPAR 信号通路
GO:0045664	神经元分化调控	GO:0019395	脂肪酸氧化
GO:0034440	脂质氧化	GO:0072329	一元羧酸降解

E14 vs E18		E14 vs W6
ID	功能描述	ID	功能描述
GO:0009891	生物合成过程的正向调控	GO:0044281	小分子代谢过程
GO:0051649	细胞内定域化建立	mmu01100	代谢途径
GO:0045595	细胞分化调控	GO:0006629	脂质代谢过程
GO:0033554	对压力的细胞应激	GO:0055114	氧化还原过程
GO:0022008	神经发生	GO:0006082	有机酸新陈代谢
GO:0048699	神经元产生	GO:0043436	酮酸代谢
GO:0030030	细胞投影组织	GO:0044255	细胞内脂质代谢
GO:0120036	质膜界细胞投影组织	GO:0019752	羧酸代谢过程
GO:0030182	神经元分化	GO:0032787	一元羧酸代谢过程
GO:0048666	神经元发育	GO:0051186	辅因子代谢
GO:0009790	胚胎发育	GO:0006631	脂肪酸代谢过程
GO:0060284	调控细胞发育	GO:0016042	脂肪分解
GO:0031175	神经元投影发育	GO:0016054	有机酸分解过程
GO:0051960	神经系统发育调节	GO:0046395	羧酸分解过程
GO:0007417	中枢神经系统发育	GO:0044242	细胞脂质降解
GO:0050767	神经形成调控	mmu03320	PPAR 信号通路
GO:0045664	神经元分化调控	GO:0019395	脂肪酸氧化
GO:0034440	脂质氧化	GO:0072329	一元羧酸降解

GEO Dataset Transcriptomics Analysis for Early Gestational Fetal Scarless Healing Pattern of Mice

胎儿早期小鼠无疤痕愈合的数据转录组学分析

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 6

References 23

Related Articles 0

Recommended Articles

Metrics

Comments