AbstractBone marrow-derived mesenchymal stem cells (BMSCs) exhibit multi-lineage differentiation potential and robust proliferative capacity. The late stage of differentiation signifies the functional maturation and characterization of specific cell lineages, which is crucial for studying lineage-specific differentiation mechanisms.

摘要骨髓间充质干细胞（BMSCs）具有多谱系分化潜能和强大的增殖能力。分化的晚期意味着特定细胞谱系的功能成熟和表征，这对于研究谱系特异性分化机制至关重要。

However, the molecular processes governing late-stage BMSC differentiation remain poorly understood. This study aimed to elucidate the key biological processes involved in late-stage BMSC differentiation. Publicly available transcriptomic data from human BMSCs were analyzed after approximately 14 days of osteogenic, adipogenic, and chondrogenic differentiation.

然而，控制晚期BMSC分化的分子过程仍然知之甚少。本研究旨在阐明晚期BMSC分化中涉及的关键生物学过程。在成骨，脂肪形成和软骨形成分化约14天后，分析了来自人BMSC的公开可用的转录组数据。

Thirty-one differentially expressed genes (DEGs) associated with differentiation were identified. Pathway enrichment analysis indicated that the DEGs were involved in extracellular matrix (ECM)-receptor interactions, focal adhesion, and glycolipid biosynthesis, a ganglion series process. Subsequently, the target genes were validated using publicly available single-cell RNA-seq data from mouse BMSCs.

鉴定了31个与分化相关的差异表达基因（DEG）。通路富集分析表明，DEGs参与细胞外基质（ECM）-受体相互作用，粘着斑和糖脂生物合成，这是一个神经节系列过程。随后，使用来自小鼠BMSC的公开可用的单细胞RNA-seq数据验证靶基因。

Lamc1 exhibited predominant distribution in adipocytes and osteoblasts, primarily during the G2/M phase. Tln2 and Hexb were expressed in chondroblasts, osteoblasts, and adipocytes, while St3gal5 was abundantly distributed in stem cells. Cell communication analysis identified two receptors that interact with LAMCI.

。Tln2和Hexb在成软骨细胞，成骨细胞和脂肪细胞中表达，而St3gal5在干细胞中大量分布。细胞通讯分析确定了两种与LAMCI相互作用的受体。

q-PCR results confirmed the upregulation of Lamc1, Tln2, Hexb, and St3gal5 during osteogenic differentiation and their downregulation during adipogenic differentiation. Knockdown of Lamc1 inhibited adipogenic and osteogenic differentiation. In conclusion, this study identified four genes, Lamc1, Tln2, Hexb, and St3gal5, that may play important roles in the late-stage differentiat.

q-PCR结果证实了成骨分化过程中Lamc1，Tln2，Hexb和St3gal5的上调及其在成脂分化过程中的下调。敲低Lamc1抑制脂肪形成和成骨分化。总之，这项研究确定了四个基因Lamc1，Tln2，Hexb和St3gal5，它们可能在晚期分化中起重要作用。

IntroductionMesenchymal stem cells (MSCs) are pluripotent that can be obtained from various tissues, umbilical cord, amniotic fluid, and placenta1,2,3,4. It is capable of expanding and differentiating in vitro into a variety of mesodermal-type lineages, including bone, adipose, cartilage, muscle, tendon, and stroma, supporting hematopoiesis and the vascular system, and undergoes migration and paracrine signaling, which is not only crucial in embryonic development but also plays an important role in tissue homeostasis and repair throughout the life of an organism5,6.

引言间充质干细胞（MSCs）是多能的，可以从各种组织，脐带，羊水和胎盘中获得1,2,3,4。它能够在体外扩增和分化成多种中胚层类型的谱系，包括骨骼，脂肪，软骨，肌肉，肌腱和基质，支持造血和血管系统，并经历迁移和旁分泌信号传导，这不仅对胚胎发育至关重要，而且在生物体的整个生命过程中在组织稳态和修复中发挥重要作用5,6。

MSCs from different sources exhibit different differentiation tendencies, and studies have shown that BMSCs exhibit greater APL activity, calcium deposition, and transformation capacity at an earlier age,compared with adipose-derived MSCs7. Therefore, BMSCs were chosen for studying the molecular mechanisms of osteogenic differentiation.Key transcription factors for osteoblast differentiation are required for the expression of osteoblast-specific genes, including Runt-associated transcription factor 2 (Runx2) and osteocalcin (Ocn), alkaline phosphatase (ALP), type I collagen, bone bridging proteins, and bone sialic acid protein8,9,10,11,12,13.

来自不同来源的MSCs表现出不同的分化趋势，研究表明，与脂肪来源的MSCs相比，BMSCs在较早的年龄表现出更高的APL活性，钙沉积和转化能力7。因此，选择BMSCs来研究成骨分化的分子机制。成骨细胞分化的关键转录因子是成骨细胞特异性基因表达所必需的，包括矮子相关转录因子2（Runx2）和骨钙素（Ocn），碱性磷酸酶（ALP），I型胶原，骨桥接蛋白和骨唾液酸蛋白8,9,10,11,12,13。

Bone morphogenetic proteins (BMPs), especially BMP-2, BMP-4, and BMP-7, activate the Smad signaling pathway, which in turn leads to the expression of Runx2 and Ocn and inhibits adipogenic differentiation14,15,16. In addition to BMP, the Wnt/\(\beta \)-catenin signaling pathway plays a key role in osteoblast differentiation17.

骨形态发生蛋白（BMPs），特别是BMP-2，BMP-4和BMP-7，激活Smad信号通路，进而导致Runx2和Ocn的表达，并抑制脂肪形成分化14,15,16。除BMP外，Wnt/\（\β\）-连环蛋白信号通路在成骨细胞分化中起关键作用17。

Activation of this pathway leads to the accumulation of \(\beta \)-catenin in the cytoplasm, which then translocates to the nucleus, activates the transcription of osteoblast-specific genes, and inhibits adipogenesis. On the other hand, adipocyte d.

该途径的激活导致细胞质中β-连环蛋白的积累，然后转移到细胞核，激活成骨细胞特异性基因的转录，并抑制脂肪形成。另一方面，脂肪细胞d。

Data availibility

可用数据

The datasets covered in this reasearch are all publicly available transcriptomic data from the Gene Expression Omnibus (GEO). Ullah M, Sittinger M, Ringe J. Transdifferentiation of adipogenically differentiated cells into osteogenically or chondrogenically differentiated cells: phenotype switching via dedifferentiation.

本研究涵盖的数据集都是来自Gene Expression Omnibus（GEO）的公开转录组数据。Ullah M，Sittinger M，Ringe J.脂肪分化细胞向成骨或软骨分化细胞的转分化：通过去分化进行表型转换。

Int J Biochem Cell Biol. 2014 Jan;46:124-37. doi: 10.1016/j.biocel.2013.11.010. Epub 2013 Nov 22. GSE36923. Tomaru Y, Hasegawa R, Suzuki T, Sato T, Kubosaki A, Suzuki M, Kawaji H, Forrest AR, Hayashizaki Y; FANTOM Consortium; Shin JW, Suzuki H. A transient disruption of fibroblastic transcriptional regulatory network facilitates trans-differentiation.

Int J生物化学细胞生物学。2014年1月；46:124-37。doi:10.1016/j.biocel.2013.11.010。Epub 2013年11月22日。GSE36923。Tomaru Y，Hasegawa R，Suzuki T，Sato T，Kubosaki A，Suzuki M，Kawaji H，Forrest AR，Hayashizaki Y；FANTOM财团；Shin JW，Suzuki H.成纤维细胞转录调控网络的瞬时破坏促进了转分化。

Nucleic Acids Res. 2014 Aug;42(14):8905-13. doi: 10.1093/nar/gku567. Epub 2014 Jul 10. GSE44303. Huynh NPT, Zhang B, Guilak F. High-depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis. FASEB J. 2019 Jan;33(1):358-372. doi: 10.1096/fj.201800534R.

；42（14）：8905-13。doi:10.1093/nar/gku567。Epub 2014年7月10日。GSE44303。Huynh NPT，Zhang B，Guilak F。高深度转录组学分析揭示了软骨形成过程中人间充质干细胞的时间基因特征。FASEB J.2019年1月；33（1）：358-372。doi:10.1096/fj.201800534R。

Epub 2018 Jul 9. GSE109503. Somoza RA, Correa D, Labat I, Sternberg H, Forrest ME, Khalil AM, West MD, Tesar P, Caplan AI. Transcriptome-Wide Analyses of Human Neonatal Articular Cartilage and Human Mesenchymal Stem Cell-Derived Cartilage Provide a New Molecular Target for Evaluating Engineered Cartilage.

Epub 2018年7月9日。GSE109503。Somoza RA，Correa D，Labat I，Sternberg H，Forrest ME，Khalil AM，West MD，Tesar P，Caplan AI。人类新生儿关节软骨和人间充质干细胞衍生软骨的转录组范围分析为评估工程化软骨提供了新的分子靶点。

Tissue Eng Part A. 2018 Feb;24(3-4):335-350. doi: 10.1089/ten.TEA.2016.0559. Epub 2017 Jul 28.GSE140861. Dani N, Olivero M, Mareschi K, van Duist MM, Miretti S, Cuvertino S, Patané S, Calogero R, Ferracini R, Scotlandi K, Fagioli F, Di Renzo MF. The MET oncogene transforms human primary bone-derived cells into osteosarcomas by targeting committed osteo-progenitors.

Tissue Eng Part A.2018年2月；24（3-4）：335-350。doi:10.1089/十。TEA.2016.0559。。Dani N，Olivero M，Mareschi K，van Duist MM，Miretti S，Cuvertino S，PatanéS，Calogero R，Ferracini R，Scotlandi K，Fagioli F，Di Renzo MF。MET致癌基因通过靶向定向骨祖细胞将人原代骨衍生细胞转化为骨肉瘤。

J Bone Miner Res. 2012 Jun;27(6):1322-34. doi: 10.1002/jbmr.1578. GSE28205. Alves RD, Eijken M, van de Peppel J, van Leeuwen JP. Calci.

《骨矿工研究杂志》2012年6月；27(6):1322-34.doi:10.1002/jbmr.1578。GSE28205.Alves RD，Eijken M，van de Peppel J，van Leeuwen JP。

ReferencesJohnson, J. et al. From mesenchymal stromal cells to engineered extracellular vesicles: A new therapeutic paradigm. Front. Cell Dev. Biol. 9, 705676 (2021).PubMed

参考文献Johnson，J。等人，从间充质基质细胞到工程细胞外囊泡：一种新的治疗范例。正面。细胞开发生物学。9705676（2021）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen, Q. et al. Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts?. Cell Death Differ. 23(7), 1128–1139 (2016).CAS

Chen，Q。等人。间充质干细胞的命运决定：脂肪细胞还是成骨细胞？。细胞死亡不同。23（7），1128-1139（2016）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jain, M. et al. Amniotic fluid mesenchymal stromal cells derived from fetuses with isolated cardiac defects exhibit decreased proliferation and cardiomyogenic potential. Biology 12(4), 552 (2023).CAS

。生物学12（4），552（2023）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Biswas, A. et al. Human placenta/umbilical cord derivatives in regenerative medicine—Prospects and challenges. Biomater. Sci. 11(14), 4789–4821 (2023).CAS

Biswas，A.等人，《人类胎盘/脐带衍生物在再生医学中的前景和挑战》。生物计。科学。11（14），4789-4821（2023）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liebig, B. E. et al. The platelet-rich plasma and mesenchymal stem cell milieu: A review of therapeutic effects on bone healing. J. Orthop. Res. 38(12), 2539–2550 (2020).PubMed

Liebig，B.E。等人。富含血小板的血浆和间充质干细胞环境：对骨愈合的治疗效果的综述。J、 骨科。第38（12）号决议，第2539–2550（2020）号决议。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jiang, Y., Zhang, P., Zhang, X., et al. Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis. Cell Prolif. 54(1), (2021).Mohamed-Ahmed, S. et al. Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison[J]. Stem Cell Res. Therapy 9(1), 168 (2018).CAS .

Jiang，Y.，Zhang，P.，Zhang，X。等。间充质干细胞移植治疗骨质疏松症的进展。细胞增殖。54（1），（2021年）。Mohamed Ahmed，S.等。脂肪来源和骨髓间充质干细胞：供体匹配比较〔J〕。干细胞研究治疗9（1），168（2018）。CAS。

Google Scholar

谷歌学者

Liu, D. D. et al. RUNX2 regulates osteoblast differentiation via the BMP4 signaling pathway. J. Dent. Res. 101(10), 1227–1237 (2022).CAS

Liu，D.D.等人，RUNX2通过BMP4信号通路调节成骨细胞分化。J、 凹痕。第101（10）号决议，第1227–1237（2022）号决议。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Komori, T. Functions of osteocalcin in bone, pancreas, testis, and muscle. Int. J. Mol. Sci. 21(20), 7513 (2020).CAS

Komori，T。骨钙素在骨骼，胰腺，睾丸和肌肉中的功能。Int.J.Mol.Sci。21（20），7513（2020）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fisher, L. A. B. & Schöck, F. The unexpected versatility of ALP/Enigma family proteins. Front. Cell Dev. Biol. 10, 963608 (2022).PubMed

Fisher，L.A.B。＆Schöck，F。ALP/Enigma家族蛋白出乎意料的多功能性。正面。细胞开发生物学。。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kriegel, A. et al. Bone sialoprotein immobilized in collagen type I enhances bone regeneration in vitro and in vivo. Int. J. Bioprint. 8(3), 591 (2022).CAS

Kriegel，A。等人。固定在I型胶原中的骨唾液蛋白在体外和体内增强骨再生。《国际生物印刷杂志》8（3），591（2022）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wei, J. et al. Glucose uptake and Runx2 synergize to orchestrate osteoblast differentiation and bone formation. Cell 161(7), 1576–1591 (2015).CAS

Wei，J。等人。葡萄糖摄取和Runx2协同作用以协调成骨细胞分化和骨形成。细胞161（7），1576-1591（2015）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Neve, A., Corrado, A. & Cantatore, F. P. Osteocalcin: Skeletal and extra-skeletal effects. J. Cell. Physiol. 228(6), 1149–1153 (2013).CAS

Neve，A.，Corrado，A。＆Cantatore，F.P。骨钙素：骨骼和骨骼外效应。J、 细胞。生理学。。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Tóth, F. et al. Effect of inducible bone morphogenetic protein 2 expression on the osteogenic differentiation of dental pulp stem cells in vitro. Bone 132, 115214 (2020).PubMed

Tóth，F。等人。诱导型骨形态发生蛋白2表达对牙髓干细胞体外成骨分化的影响。骨骼132115214（2020）。PubMed出版社

Google Scholar

谷歌学者

Cheng, H. et al. Bone morphogenetic protein 4 rescues the bone regenerative potential of old muscle-derived stem cells via regulation of cell cycle inhibitors. Stem Cell Res. Ther. 13(1), 385 (2022).CAS

Cheng，H。等人。骨形态发生蛋白4通过调节细胞周期抑制剂来挽救旧肌肉干细胞的骨再生潜力。干细胞研究。13（1），385（2022）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bharadwaz, A. & Jayasuriya, A. C. Osteogenic differentiation cues of the bone morphogenetic protein-9 (BMP-9) and its recent advances in bone tissue regeneration[J]. Mater. Sci. Eng. C Mater. Biol. Appl. 120, 111748 (2021).CAS

Bharadwaz，A.＆Jayasuriya，A.C。骨形态发生蛋白-9（BMP-9）的成骨分化线索及其在骨组织再生中的最新进展〔J〕。马特。科学。工程材料。生物学应用。120111748（2021）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Deng, L. et al. MFN2 knockdown promotes osteogenic differentiation of iPSC-MSCs through aerobic glycolysis mediated by the Wnt/\(\beta \)-catenin signaling pathway[J]. Stem Cell Res. Ther. 13(1), 162 (2022).CAS

Deng，L。等人。MFN2敲低通过Wnt/\（\β\）-连环蛋白信号通路介导的有氧糖酵解促进iPSC-MSCs的成骨分化。干细胞研究。13（1），162（2022）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cao, Y. et al. PPAR\(\gamma \) as a potential target for adipogenesis induced by fine particulate matter in 3T3-L1 preadipocytes. Environ. Sci. Technol. 57(20), 7684–7697 (2023).ADS

Cao，Y。等人。PPAR（γ）作为3T3-L1前脂肪细胞中细颗粒物诱导脂肪形成的潜在靶标。环境。科学。技术。57（20），7684–7697（2023）。广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu, C. et al. CHD7 regulates bone-fat balance by suppressing PPAR-\(\gamma \) signaling. Nat. Commun. 13(1), 1989 (2022).ADS

Liu，C。等人。CHD7通过抑制PPAR-（γ）信号传导来调节骨脂肪平衡。国家公社。13（1），1989（2022）。广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liu, Z.-Z. et al. Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3. Autophagy 17(10), 2766–2782 (2021).CAS

Liu，Z.-Z.等人。自噬受体OPTN（optineurin）通过清除FABP3来调节衰老过程中间充质干细胞的命运和骨脂肪平衡。自噬17（10），2766-2782（2021）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Benayahu, D., Wiesenfeld, Y. & Sapir-Koren, R. How is mechanobiology involved in mesenchymal stem cell differentiation toward the osteoblastic or adipogenic fate?. J. Cell. Physiol. 234(8), 12133–12141 (2019).CAS

？。J、 细胞。生理学。234（8），12133–12141（2019）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Levi, N. et al. The ECM path of senescence in aging: Components and modifiers. FEBS J. 287(13), 2636–2646 (2020).CAS

Levi，N.等人。衰老中衰老的ECM途径：成分和修饰剂。FEBS J.287（13），2636–2646（2020）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yanli, Z. et al. MY-1-loaded nano-hydroxyapatite accelerated bone regeneration by increasing type III collagen deposition in early-stage ECM via a Hsp47-dependent mechanism. Adv. Healthc. Mater. 12(20), e2300332 (2023).PubMed

Yanli，Z。等人。负载MY-1的纳米羟基磷灰石通过Hsp47依赖性机制增加早期ECM中的III型胶原沉积来加速骨再生。健康顾问。马特。12（20），e2300332（2023）。PubMed出版社

Google Scholar

谷歌学者

Wang, Y. et al. Impact of fibronectin knockout on proliferation and differentiation of human infrapatellar fat pad-derived stem cells. Front. Bioeng. Biotechnol. 7, 321 (2019).PubMed

Wang，Y。等。纤维连接蛋白敲除对人髌下脂肪垫来源干细胞增殖和分化的影响。正面。生物能源。生物技术。7321（2019）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Xiong, X. et al. Extracellular matrix derived from human urine-derived stem cells enhances the expansion, adhesion, spreading, and differentiation of human periodontal ligament stem cells. Stem Cell Res. Ther. 10(1), 396 (2019).CAS

熊，X。等。源自人尿源性干细胞的细胞外基质增强人牙周膜干细胞的扩增，粘附，扩散和分化。干细胞研究。10（1），396（2019）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cai, R. et al. Matrices secreted during simultaneous osteogenesis and adipogenesis of mesenchymal stem cells affect stem cells differentiation. Acta Biomater. 35, 185–193 (2016).CAS

Cai，R。等人。间充质干细胞同时成骨和成脂过程中分泌的基质影响干细胞分化。生物计量学报。35185-193（2016）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zhang, D. et al. CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin \(\alpha \)5 expression. Cell Death Differ. 28(1), 283–302 (2021).PubMed

Zhang，D。等人。CircRNA-vgll3通过调节miRNA依赖性整合素（α）5的表达促进脂肪间充质干细胞的成骨分化。细胞死亡不同。28（1），283-302（2021）。PubMed出版社

Google Scholar

谷歌学者

Morandi, E. M. et al. ITGAV and ITGA5 diversely regulate proliferation and adipogenic differentiation of human adipose derived stem cells. Sci. Rep. 6, 28889 (2016).ADS

Morandi，E.M.等人，ITGAV和ITGA5对人脂肪干细胞的增殖和成脂分化有不同的调节作用。科学。代表62889（2016）。广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhu, J., Li, J., Yao, T., et al. Analysis of the role of irisin receptor signaling in regulating osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells. Biotechnol. Genet. Eng. Rev. 1–24 (2023).Hu, M., Ling, Z. & Ren, X. Extracellular matrix dynamics: Tracking in biological systems and their implications.

Zhu，J.，Li，J.，Yao，T。等。分析鸢尾素受体信号传导在调节骨髓间充质干细胞成骨/成脂分化中的作用。生物技术。基因。工程版本1-24（2023）。。

J. Biol. Eng. 16, 13 (2022).CAS .

J.生物学。工程16、13（2022）。CAS。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schlesinger, P. H. et al. Cellular and extracellular matrix of bone, with principles of synthesis and dependency of mineral deposition on cell membrane transport. Am. J. Physiol. Cell Physiol. 318(1), C111–C124 (2020).CAS

Schlesinger，P.H.等人，《骨的细胞和细胞外基质，合成原理和矿物质沉积对细胞膜运输的依赖性》。Am.J.Physiol。细胞生理学。318（1），C111–C124（2020）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

El-Rashidy, A. A. et al. Effect of polymeric matrix stiffness on osteogenic differentiation of mesenchymal stem/progenitor cells: Concise review. Polymers 13(17), 2950 (2021).CAS

El Rashidy，A.A.等人。聚合物基质刚度对间充质干/祖细胞成骨分化的影响：简要综述。聚合物13（17），2950（2021）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen, Y. et al. ECM scaffolds mimicking extracellular matrices of endochondral ossification for the regulation of mesenchymal stem cell differentiation. Acta Biomater. 114, 158–169 (2020).CAS

。生物计量学报。114158-169（2020）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wan, H.-Y. et al. Dextran sulfate-amplified extracellular matrix deposition promotes osteogenic differentiation of mesenchymal stem cells. Acta Biomater. 140, 163–177 (2022).CAS

Wan，H.-Y.等人。硫酸葡聚糖扩增的细胞外基质沉积促进间充质干细胞的成骨分化。生物计量学报。140163-177（2022）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu, X. et al. Type I collagen inhibits adipogenic differentiation via YAP activation in vitro. J. Cell. Physiol. 235(2), 1821–1837 (2020).CAS

Liu，X。等人。I型胶原蛋白通过体外YAP激活抑制脂肪形成分化。J、 细胞。生理学。235（2），1821-1837（2020）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Jiang, Y. & Tuan, R. S. Bioactivity of human adult stem cells and functional relevance of stem cell-derived extracellular matrix in chondrogenesis. Stem Cell Res. Ther. 14(1), 160 (2023).CAS

Jiang，Y。＆Tuan，R.S。人成体干细胞的生物活性和干细胞衍生的细胞外基质在软骨形成中的功能相关性。干细胞研究。14（1），160（2023）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lin, X. et al. The bone extracellular matrix in bone formation and regeneration. Front. Pharmacol. 11, 757 (2020).CAS

Lin，X。等人。骨形成和再生中的骨细胞外基质。正面。药理学。11757（2020）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

O’Doherty, M. et al. Improving the intercellular uptake and osteogenic potency of calcium phosphate via nanocomplexation with the RALA peptide. Nanomaterials (Basel, Switzerland) 10(12), 2442 (2020).PubMed

O'Doherty，M。等人。通过与RALA肽的纳米复合来改善磷酸钙的细胞间摄取和成骨效力。纳米材料（瑞士巴塞尔）10（12），2442（2020）。PubMed出版社

Google Scholar

谷歌学者

Chen, H. Adipose extracellular matrix deposition is an indicator of obesity and metabolic disorders. J. Nutr. Biochem. 111, 109159 (2023).CAS

Chen，H。脂肪细胞外基质沉积是肥胖和代谢紊乱的指标。J、 营养。生物化学。111109159（2023）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Ullah, M., Sittinger, M. & Ringe, J. Extracellular matrix of adipogenically differentiated mesenchymal stem cells reveals a network of collagen filaments, mostly interwoven by hexagonal structural units. Matrix Biol. 32(7–8), 452–465 (2013).CAS

Ullah，M.，Sittinger，M。＆Ringe，J。脂肪分化的间充质干细胞的细胞外基质揭示了胶原丝网络，主要由六角形结构单元交织而成。。32（7-8），452-465（2013）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen, C., Jiang, Z. & Yang, G. Laminins in osteogenic differentiation and pluripotency maintenance. Differentiation 114, 13–19 (2020).CAS

。分化114,13-19（2020）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yap, L. Laminins in cellular differentiation. Trends Cell Biol. 29(12), 987–1000 (2019).CAS

Yap，L。层粘连蛋白在细胞分化中的作用。趋势细胞生物学。29（12），987-1000（2019）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sun, M. Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin \(\alpha \)5. Stem Cell Res. Ther. 9(1), 52 (2018).PubMed

Sun，M。细胞外基质刚度控制整合素（α）5介导的间充质干细胞的成骨分化。干细胞研究。9（1），52（2018）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang, Y. et al. Mesenchymal Stem cell-derived extracellular matrix enhances chondrogenic phenotype of and cartilage formation by encapsulated chondrocytes in vitro and in vivo. Acta Biomater. 69, 71–82 (2019).

Yang，Y。等人。间充质干细胞衍生的细胞外基质在体外和体内通过包裹的软骨细胞增强软骨形成表型和软骨形成。生物计量学报。69,71-82（2019）。

Google Scholar

谷歌学者

Henry, M. D. et al. Distinct roles for dystroglycan, \(\beta \)1 integrin and perlecan in cell surface laminin organization. J. Cell Sci. 114(Pt 6), 1137–1144 (2001).CAS

Henry，M.D.等人。肌营养不良蛋白聚糖、\（\β\）1整合素和perlecan在细胞表面层粘连蛋白组织中的不同作用。J、 细胞科学。114（Pt 6），1137–1144（2001）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Souza, A. T. P. et al. The extracellular matrix protein Agrin is expressed by osteoblasts and contributes to their differentiation. Cell Tissue Res. 386(2), 335–347 (2021).CAS

Souza，A.T.P.等人。细胞外基质蛋白Agrin由成骨细胞表达并有助于其分化。细胞组织研究386（2），335-347（2021）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Eldridge, S. et al. Agrin mediates chondrocyte homeostasis and requires both LRP4 and \(\alpha \)-dystroglycan to enhance cartilage formation in vitro and in vivo. Ann. Rheum. Dis. 75(6), 1228–1235 (2016).CAS

。安。瑞姆。Dis。75（6），1228-1235（2016）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

in, S. H., Kim, S. K. & Lee, S. B. M. leprae interacts with the human epidermal keratinocytes, neonatal (HEKn) via the binding of laminin-5 with \(\alpha \)-dystroglycan, integrin-\(\beta \)1, or -\(\beta \)4[J]. PLoS Negl. Trop. Dis. 13(6), e0007339 (2019).

in，S.H.，Kim，S.K.＆Lee，S.B.M.麻风菌通过层粘连蛋白-5与\（\α\）-营养不良聚糖，整合素\（\β\）1或\（\β\）4的结合与人表皮角质形成细胞，新生儿（HEKn）相互作用[J]。公共科学图书馆。托普。Dis。13（6），e0007339（2019）。

Google Scholar

谷歌学者

Download referencesFundingThis research was supported by the National Natural Science Foundation of China (Grant numbers 81960171 and 82360167) and Guizhou Provincial Science and Technology Program (Guizhou Science and Technology Foundation-ZK[2022] General 620).Author informationAuthor notesThese authors contributed equally: Lixia Zhao and Shuai Liu.Authors and AffiliationsBioengineering College, Zunyi Medical University, 368 Jinwan Road, Zhuhai, 519090, Guangdong, ChinaLixia Zhao, Shuai Liu, Yanqiu Peng & Jian ZhangAuthorsLixia ZhaoView author publicationsYou can also search for this author in.

。作者信息作者注意到这些作者做出了同样的贡献：赵丽霞和刘帅。作者和所属单位遵义医科大学工程学院，珠海金湾路368号，广东519090，赵丽霞，刘帅，彭燕秋，张健作者赵丽霞查看作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarShuai LiuView author publicationsYou can also search for this author in

PubMed Google ScholarShuai LiuView作者出版物您也可以在

PubMed Google ScholarYanqiu PengView author publicationsYou can also search for this author in

PubMed Google ScholarYanqiu PengView作者出版物您也可以在

PubMed Google ScholarJian ZhangView author publicationsYou can also search for this author in

PubMed Google ScholarJian ZhangView作者出版物您也可以在

PubMed Google ScholarContributionsL.Z. and S.L. wrote the main manuscript text and Y.P. typesetted and checked the manuscripts. J.Z. led and supervised the planning and execution of the experiments. All authors reviewed the manuscript.Corresponding authorCorrespondence to

PubMed谷歌学术贡献l。Z、 S.L.撰写了主要的手稿文本，Y.P.排版并检查了手稿。J、 Z.领导并监督实验的计划和执行。所有作者都审阅了手稿。对应作者对应

Jian Zhang.Ethics declarations

张健。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Additional informationPublisher's noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary InformationSupplementary Information.Rights and permissions

Additional informationPublisher的noteSpringer Nature在已发布地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充信息。权限和权限

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

开放获取本文是根据知识共享署名非商业性NoDerivatives 4.0国际许可证授权的，该许可证允许以任何媒介或格式进行任何非商业性使用，共享，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出您是否修改了许可材料。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

根据本许可证，您无权共享源自本文或其部分的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可证中，除非该材料的信用额度中另有说明。。

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleZhao, L., Liu, S., Peng, Y. et al. Lamc1 promotes osteogenic differentiation and inhibits adipogenic differentiation of bone marrow-derived mesenchymal stem cells.

转载和许可本文引用本文Zhao，L.，Liu，S.，Peng，Y。等人。Lamc1促进成骨分化并抑制骨髓间充质干细胞的成脂分化。

Sci Rep 14, 19592 (2024). https://doi.org/10.1038/s41598-024-69629-4Download citationReceived: 15 May 2024Accepted: 07 August 2024Published: 23 August 2024DOI: https://doi.org/10.1038/s41598-024-69629-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Sci Rep 1419592（2024）。https://doi.org/10.1038/s41598-024-69629-4Download引文接收日期：2024年5月15日接受日期：2024年8月7日发布日期：2024年8月23日OI：https://doi.org/10.1038/s41598-024-69629-4Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

KeywordsMesenchymal stem cellOsteogenesisAdipogenesisLamininSingle-cell RNA-seq

关键词间充质干纤维干细胞生成性脂肪生成层粘连单细胞RNA-seq

CommentsBy submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

评论通过提交评论，您同意遵守我们的条款和社区指南。如果您发现有虐待行为或不符合我们的条款或准则，请将其标记为不合适。