CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes

Neuron. 2020 Aug 5;107(3):436-453.e12. doi: 10.1016/j.neuron.2020.05.014. Epub 2020 Jun 1.


New methods for investigating human astrocytes are urgently needed, given their critical role in the central nervous system. Here we show that CD49f is a novel marker for human astrocytes, expressed in fetal and adult brains from healthy and diseased individuals. CD49f can be used to purify fetal astrocytes and human induced pluripotent stem cell (hiPSC)-derived astrocytes. We provide single-cell and bulk transcriptome analyses of CD49f+ hiPSC-astrocytes and demonstrate that they perform key astrocytic functions in vitro, including trophic support of neurons, glutamate uptake, and phagocytosis. Notably, CD49f+ hiPSC-astrocytes respond to inflammatory stimuli, acquiring an A1-like reactive state, in which they display impaired phagocytosis and glutamate uptake and fail to support neuronal maturation. Most importantly, we show that conditioned medium from human reactive A1-like astrocytes is toxic to human and rodent neurons. CD49f+ hiPSC-astrocytes are thus a valuable resource for investigating human astrocyte function and dysfunction in health and disease.

Keywords: A1 reactive astrocytes; CD49f; FACS purification; astrocytes; induced pluripotent stem cells; neurodegeneration; neurotoxicity.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / physiology
  • Biomarkers / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Glutamic Acid / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Integrin alpha6 / metabolism*
  • Mice
  • Patch-Clamp Techniques
  • Phagocytosis / physiology
  • RNA-Seq
  • Single-Cell Analysis


  • Biomarkers
  • Integrin alpha6
  • Glutamic Acid