Disease Modeling and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore, 117543, Singapore.
Stem Cell Res Ther. 2019 Nov 21;10(1):336. doi: 10.1186/s13287-019-1451-2.
Development of the complex human heart is tightly regulated at multiple levels, maintaining multipotency and proliferative state in the embryonic cardiovascular progenitors and thereafter suppressing progenitor characteristics to allow for terminal differentiation and maturation. Small regulatory microRNAs (miRNAs) are at the level of post-transcriptional gene suppressors, which enhance the degradation or decay of their target protein-coding mRNAs. These miRNAs are known to play roles in a large number of biological events, cardiovascular development being no exception. A number of critical cardiac-specific miRNAs have been identified, of which structural developmental defects have been linked to dysregulation of miRNAs in the proliferating cardiac stem cells. These miRNAs present in the stem cell niche are lost when the cardiac progenitors terminally differentiate, resulting in the postnatal mitotic arrest of the heart. Therapeutic applications of these miRNAs extend to the realm of heart failure, whereby the death of heart cells in the ageing heart cannot be replaced due to the arrest of cell division. By utilizing miRNA therapy to control cell cycling, the regenerative potential of matured myocardium can be restored. This review will address the various cardiac progenitor-related miRNAs that control the development and proliferative potential of the heart.
人类心脏的发育是在多个层次上受到严格调控的，在胚胎心血管祖细胞中维持多能性和增殖状态，然后抑制祖细胞特征，以允许终末分化和成熟。小的调节 microRNAs（miRNAs）处于转录后基因抑制物的水平，增强其靶蛋白编码 mRNA 的降解或衰减。这些 miRNAs 已知在大量的生物学事件中发挥作用，心血管发育也不例外。已经确定了许多关键的心脏特异性 miRNAs，其中结构发育缺陷与增殖性心脏干细胞中 miRNAs 的失调有关。当心脏祖细胞终末分化时，存在于干细胞龛中的这些 miRNAs 丢失，导致心脏的出生后有丝分裂停止。这些 miRNAs 的治疗应用延伸到心力衰竭领域，由于衰老心脏中心脏细胞的死亡不能由于细胞分裂的停止而被取代。通过利用 miRNA 治疗来控制细胞周期，可以恢复成熟心肌的再生潜力。这篇综述将讨论控制心脏发育和增殖潜力的各种心脏祖细胞相关 miRNA。
