Hiew Vun Vun, Teoh Peik Lin
Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.
Stem Cells Int. 2022 Aug 28;2022:2116367. doi: 10.1155/2022/2116367. eCollection 2022.
Transcriptomic analysis revealed mesenchymal stem/stromal cells (MSCs) from various origins exhibited distinct gene and protein expression profiles dictating their biological properties. Although collagen type 1 (COL) has been widely studied in bone marrow MSCs, its role in regulating cell fate of Wharton jelly- (WJ-) MSCs is not well understood. In this study, we investigated the effects of collagen on the characteristics of WJ-MSCs associated with proliferation, surface markers, adhesion, migration, self-renewal, and differentiation capabilities through gene expression studies. The isolated WJ-MSCs expressed positive surface markers but not negative markers. Gene expression profiles showed that COL not only maintained the pluripotency, self-renewal, and immunophenotype of WJ-MSCs but also primed cells toward lineage differentiations by upregulating and genes. Upon osteoinduction, WJ-MSC-COL underwent osteogenesis by switching on the transcription of and followed by activation of downstream target genes such as , , , and through p38 signalling. This molecular event was also accompanied by hypomethylation at the promoter and increase of H3K9 acetylation. In conclusion, COL provides a conducive cellular environment in priming WJ-MSCs that undergo a lineage specification upon receiving an appropriate signal from extrinsic factor. These findings would contribute to better control of fate determination of MSCs for therapeutic applications related to bone disease.
转录组分析表明,来自不同来源的间充质干/基质细胞(MSC)表现出独特的基因和蛋白质表达谱,决定了它们的生物学特性。虽然I型胶原(COL)在骨髓间充质干细胞中已得到广泛研究,但其在调节华通氏胶间充质干细胞(WJ-MSC)细胞命运中的作用尚不清楚。在本研究中,我们通过基因表达研究,探讨了胶原对WJ-MSC与增殖、表面标志物、黏附、迁移、自我更新及分化能力相关特性的影响。分离出的WJ-MSC表达阳性表面标志物,而不表达阴性标志物。基因表达谱显示,COL不仅维持了WJ-MSC的多能性、自我更新和免疫表型,还通过上调相关基因促使细胞向谱系分化。在成骨诱导后,WJ-MSC-COL通过开启相关基因的转录并随后通过p38信号通路激活下游靶基因(如相关基因)来进行成骨。这一分子事件还伴随着相关启动子处的低甲基化以及H3K9乙酰化的增加。总之,COL在促使WJ-MSC方面提供了一个有利的细胞环境,WJ-MSC在从外在因子接收到适当信号后会发生谱系特化。这些发现将有助于更好地控制间充质干细胞的命运决定,以用于与骨疾病相关的治疗应用。