Mukundan Namita, Hariharan Nivedita, Sasidharan Vidyanand, Lakshmanan Vairavan, Palakodeti Dasaradhi, Jamora Colin
Integrative Chemical Biology (ICB), Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India.
Manipal Academy of Higher Education, Manipal, India.
Front Cell Dev Biol. 2024 Sep 23;12:1433142. doi: 10.3389/fcell.2024.1433142. eCollection 2024.
Post-transcriptional regulation has emerged as a key mechanism for regulating stem cell renewal and differentiation, which is essential for understanding tissue regeneration and homeostasis. Poly(A)-binding proteins are a family of RNA-binding proteins that play a vital role in post-transcriptional regulation by controlling mRNA stability and protein synthesis. The involvement of poly(A) binding proteins in a wide range of cellular functions is increasingly being investigated. In this study, we used the regenerative model planarian organism to demonstrate the critical role of poly(A)-binding protein 2 (PABP2) in regulating neoblast maintenance and differentiation. A deficit in PABP2 blocks the transition of neoblasts toward immediate early progenitors, leading to an enhanced pool of non-committed neoblasts and a decreased progenitor population. This is reflected in variations in the transcriptome profile, providing evidence of downregulation in multiple lineages. Thus, an insufficiency of PABP2 resulted in defective formation and organization of tissue, leading to abnormal regeneration. Our study reveals the essential role of PABP2 in regulating genes that mediate stem cell commitment to early progenitors during tissue regeneration.
转录后调控已成为调节干细胞自我更新和分化的关键机制,这对于理解组织再生和体内平衡至关重要。聚腺苷酸结合蛋白是一类RNA结合蛋白,通过控制mRNA稳定性和蛋白质合成在转录后调控中发挥重要作用。聚腺苷酸结合蛋白在广泛的细胞功能中的参与正越来越多地受到研究。在本研究中,我们使用再生模型涡虫来证明聚腺苷酸结合蛋白2(PABP2)在调节新生细胞维持和分化中的关键作用。PABP2的缺陷会阻止新生细胞向即时早期祖细胞的转变,导致未定向新生细胞池增加和祖细胞群体减少。这反映在转录组图谱的变化中,提供了多个谱系下调的证据。因此,PABP2的不足导致组织形成和组织异常,导致再生异常。我们的研究揭示了PABP2在调节组织再生过程中介导干细胞向早期祖细胞定向的基因中的重要作用。