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Prospectively Isolated Tetraspanin+ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration
journal contributionposted on 2023-11-14, 04:12 authored by An Zeng, Hua Li, Longhua Guo, Xin Gao, Sean McKinney, Yongfu Wang, Zulin Yu, Jungeun Park, Craig Semerad, Eric Ross, Li-Chun Cheng, Erin Davies, Kai Lei, Wei Wang, Anoja Perera, Kate HallKate Hall, Allison Peak, Andrew Box, Alejandro Sanchez Alvarado
Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue. Large-scale scRNA-seq of sorted neoblasts unveiled a novel subtype of neoblast (Nb2) characterized by high levels of PIWI-1 mRNA and protein and marked by a conserved cell-surface protein-coding gene, tetraspanin 1 (tspan-1). tspan-1-positive cells survived sub-lethal irradiation, underwent clonal expansion to repopulate whole animals, and when purified with an anti-TSPAN-1 antibody, rescued the viability of lethally irradiated animals after single-cell transplantation. The first prospective isolation of an adult PSC bridges a conceptual dichotomy between functionally and molecularly defined neoblasts, shedding light on mechanisms governing in vivo pluripotency and a source of regeneration in animals. VIDEO ABSTRACT.
Publication classificationC1.1 Refereed article in a scholarly journal
Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyCell BiologyEXCRETORY SYSTEMGENEMAINTENANCEplanariapluripotentprospective isolationregenerationsingle cell transplantationstem cellstetraspaninAnimalsArgonaute ProteinsCell CycleGene Expression RegulationHelminth ProteinsPlanariansPluripotent Stem CellsPrincipal Component AnalysisRNA InterferenceRNA, Double-StrandedRNA, HelminthRegenerationSequence Analysis, RNASingle-Cell AnalysisTetraspaninsWhole-Body IrradiationRegenerative MedicineStem Cell ResearchGenetics1 Underpinning research1.1 Normal biological development and functioningGeneric health relevance