Prospectively Isolated Tetraspanin + Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration

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 Hall, Allison Peak, Andrew Box, Alejandro Sánchez Alvarado

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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: [Figure presented] Transplantation of a single pluripotent neoblast can restore regenerative ability and viability to lethally irradiated Planaria.

Original languageEnglish (US)
Pages (from-to)1593-1608.e20
JournalCell
Volume173
Issue number7
DOIs
StatePublished - Jun 14 2018

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Keywords

  • planaria
  • pluripotent
  • prospective isolation
  • regeneration
  • single cell transplantation
  • stem cells
  • tetraspanin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zeng, A., Li, H., Guo, L., Gao, X., McKinney, S., Wang, Y., Yu, Z., Park, J., Semerad, C., Ross, E., Cheng, L. C., Davies, E., Lei, K., Wang, W., Perera, A., Hall, K., Peak, A., Box, A., & Sánchez Alvarado, A. (2018). Prospectively Isolated Tetraspanin + Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration Cell, 173(7), 1593-1608.e20. https://doi.org/10.1016/j.cell.2018.05.006