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

Cell. 2018 Jun 14;173(7):1593-1608.e20. doi: 10.1016/j.cell.2018.05.006.

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.

Keywords: planaria; pluripotent; prospective isolation; regeneration; single cell transplantation; stem cells; tetraspanin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / antagonists & inhibitors
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Cell Cycle / radiation effects
  • Gene Expression Regulation
  • Helminth Proteins / antagonists & inhibitors
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Planarians / physiology*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / transplantation
  • Principal Component Analysis
  • RNA Interference
  • RNA, Double-Stranded / metabolism
  • RNA, Helminth / chemistry
  • RNA, Helminth / isolation & purification
  • RNA, Helminth / metabolism
  • Regeneration / genetics
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Tetraspanins / genetics
  • Tetraspanins / metabolism*
  • Whole-Body Irradiation

Substances

  • Argonaute Proteins
  • Helminth Proteins
  • RNA, Double-Stranded
  • RNA, Helminth
  • Tetraspanins