School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Department of Biochemistry and Molecular Pharmacology, New York University, School of Medicine, New York, USA.
Cell Prolif. 2024 Jan;57(1):e13524. doi: 10.1111/cpr.13524. Epub 2023 Jun 25.
Adult stem cells (ASCs) are pluripotent cells with the capacity to self-renew and constantly replace lost cells due to physiological turnover or injury. Understanding the molecular mechanisms of the precise coordination of stem cell proliferation and proper cell fate decision is important to regeneration and organismal homeostasis. The planarian epidermis provides a highly tractable model to study ASC complex dynamic due to the distinct spatiotemporal differentiation stages during lineage development. Here, we identified the myosin regulatory light chain (MRLC) homologue in the Dugesia japonica transcriptome. We found high expression levels of MRLC in wound region during regeneration and also expressed in late epidermal progenitors as an essential regulator of the lineage from neoblasts to mature epidermal cells. We investigated the function of MRLC using in situ hybridization, real-time polymerase chain reaction and double fluorescent and uncovered the potential mechanism. Knockdown of MRLC leads to a remarkable increase in cell death, causes severe abnormalities during regeneration and homeostasis and eventually leads to animal death. The global decrease in epidermal cell in MRLC RNAi animals induces accelerated epidermal proliferation and differentiation. Additionally, we find that MRLC is co-expressed with cdc42 and acts cooperatively to control the epidermal lineage development by affecting cell death. Our results uncover an important role of MRLC, as an inhibitor of apoptosis, involves in epidermal development.
成体干细胞(ASCs)是多能细胞,具有自我更新的能力,并能不断取代因生理更替或损伤而丢失的细胞。了解干细胞增殖和适当细胞命运决定的精确协调的分子机制对于再生和机体稳态至关重要。由于在谱系发育过程中有明显的时空分化阶段,涡虫表皮为研究 ASC 复杂动力学提供了一个高度可行的模型。在这里,我们在日本三角涡虫转录组中鉴定了肌球蛋白调节轻链(MRLC)同源物。我们发现 MRLC 在再生过程中的伤口区域表达水平较高,并且在晚期表皮祖细胞中也表达,作为从成体干细胞到成熟表皮细胞谱系的必需调节因子。我们使用原位杂交、实时聚合酶链反应和双荧光研究了 MRLC 的功能,并揭示了其潜在的机制。MRLC 的敲低导致细胞死亡显著增加,在再生和稳态过程中引起严重异常,最终导致动物死亡。MRLC RNAi 动物中表皮细胞的全面减少会诱导表皮增殖和分化的加速。此外,我们发现 MRLC 与 cdc42 共表达,并通过影响细胞死亡来协同控制表皮谱系发育。我们的研究结果揭示了 MRLC 作为凋亡抑制剂在表皮发育中的重要作用。