Fixed single-cell transcriptomic characterization of human radial glial diversity.

Elliot R Thomsen, John K Mich, Zizhen Yao, Rebecca D Hodge, Adele M Doyle, Sumin Jang, Soraya I Shehata, Angelique M Nelson, Nadiya V Shapovalova, Boaz P Levi, Sharad Ramanathan
Author Information
  1. Elliot R Thomsen: Allen Institute for Brain Science, Seattle, Washington, USA. ORCID
  2. John K Mich: Allen Institute for Brain Science, Seattle, Washington, USA.
  3. Zizhen Yao: Allen Institute for Brain Science, Seattle, Washington, USA.
  4. Rebecca D Hodge: Allen Institute for Brain Science, Seattle, Washington, USA.
  5. Adele M Doyle: Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
  6. Sumin Jang: Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
  7. Soraya I Shehata: Allen Institute for Brain Science, Seattle, Washington, USA.
  8. Angelique M Nelson: Allen Institute for Brain Science, Seattle, Washington, USA.
  9. Nadiya V Shapovalova: Allen Institute for Brain Science, Seattle, Washington, USA.
  10. Boaz P Levi: Allen Institute for Brain Science, Seattle, Washington, USA.
  11. Sharad Ramanathan: Allen Institute for Brain Science, Seattle, Washington, USA.

Abstract

The diverse progenitors that give rise to the human neocortex have been difficult to characterize because progenitors, particularly radial glia (RG), are rare and are defined by a combination of intracellular markers, position and morphology. To circumvent these problems, we developed Fixed and Recovered Intact Single-cell RNA (FRISCR), a method for profiling the transcriptomes of individual fixed, stained and sorted cells. Using FRISCR, we profiled primary human RG that constitute only 1% of the midgestation cortex and classified them as ventricular zone-enriched RG (vRG) that express ANXA1 and CRYAB, and outer subventricular zone-localized RG (oRG) that express HOPX. Our study identified vRG and oRG markers and molecular profiles, an essential step for understanding human neocortical progenitor development. FRISCR allows targeted single-cell profiling of any tissues that lack live-cell markers.

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Grants

  1. T32 GM007598/NIGMS NIH HHS
  2. 5DP1MH099906-03/NCCDPHP CDC HHS
  3. R24 HD000836/NICHD NIH HHS
  4. DP1 MH099906/NIMH NIH HHS
  5. 5R24HD000836/NICHD NIH HHS

MeSH Term

Brain
Humans
Neuroglia
Single-Cell Analysis
Transcriptome