Lee Ji-Heon, Kim Min Sup, Lee Jin-Seop, Lee Dong Hyun, Park Chansol, Lee Dong Hyuk, Kim Eun-Young, Chung Hyung Min
R&D Center, CLECELL Inc., Seoul, Korea.
Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea.
Int J Stem Cells. 2023 May 30;16(2):145-155. doi: 10.15283/ijsc22187. Epub 2023 Feb 28.
Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed.
In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3' untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation . results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease.
Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regulate muscle and vascular differentiation during embryonic development.
在胚胎学上,中胚层发育与肌肉、血管和心脏等各种器官的发育密切相关,这些是构成身体的主要器官。然而,迄今为止,针对由先天性或后天性因素引起的中胚层发育障碍的治疗,一直依赖于手术和药物治疗来缓解症状,从根本上来说,仍需要对中胚层发育障碍进行治疗。
在我们的研究中,鉴定了在中胚层发育过程中起重要作用的微小RNA(miRNA),并评估了其发育功能。miRNA由小核苷酸组成,它们作为转录因子与3'非翻译区结合并抑制靶基因表达。我们构建了人类胚胎干细胞(hESC)敲除细胞系,并分析了在中胚层谱系中起重要作用的miR-5739的功能和特性。miR-5739作为转录因子靶向SMA、短尾T、Hand1(其控制肌肉增殖和分化)以及调节血管形成的KDR基因。结果表明其在调节肌肉增殖和分化中发挥作用。基因本体分析证实,miR-5739与调节肌肉和血管增殖及分化的基因密切相关。重要的是,在先天性肌肉疾病患者来源的体细胞中检测到miR-5739的异常表达。
我们的研究表明,miR-5739基因功能在胚胎发育过程中显著影响调节肌肉和血管分化的转录通路。