Plants continuously elaborate their bodies through post-embryonic, reiterative organ formation by apical meristems [1]. Meristems harbor stem cells, which produce daughter cells that divide repeatedly before they differentiate. How transitions between stemness, proliferation, and differentiation are precisely coordinated is not well understood, but it is known that phytohormones as well as peptide signals play important roles [2-7]. For example, in Arabidopsis thaliana root meristems, developing protophloem sieve elements (PPSEs) express the secreted CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 45 (CLE45) peptide and its cognate receptor, the leucine-rich repeat receptor kinase (LRR-RK) BARELY ANY MERISTEM 3 (BAM3). Exogenous CLE45 application or transgenically increased CLE45 dosage impairs protophloem formation, suggesting autocrine inhibition of PPSE differentiation by CLE45 signaling. Since CLE45 and BAM3 are expressed throughout PPSE development, it remains unclear how this inhibition is eventually overcome. The OCTOPUS (OPS) gene is required for proper PPSE differentiation and therefore the formation of continuous protophloem strands. OPS dosage increase can mend the phenotype of other mutants that display protophloem development defects in association with CLE45-BAM3 hyperactivity [8, 9]. Here, we provide evidence that OPS protein promotes differentiation of developing PPSEs by dampening CLE45 perception. This markedly quantitative antagonism is likely mediated through direct physical interference of OPS with CLE45 signaling component interactions. Moreover, hyperactive OPS confers resistance to other CLE peptides, and ectopic OPS overexpression triggers premature differentiation throughout the root. Our results thus reveal a novel mechanism in PPSE transition toward differentiation, wherein OPS acts as an "insulator" to antagonize CLE45 signaling.