2. Academic Validation
  3. Defining the Teratoma as a Model for Multi-lineage Human Development

Defining the Teratoma as a Model for Multi-lineage Human Development

  • Cell. 2020 Nov 25;183(5):1402-1419.e18. doi: 10.1016/j.cell.2020.10.018.
Daniella McDonald 1,  Yan Wu 2,  Amir Dailamy 2,  Justin Tat 3,  Udit Parekh 4,  Dongxin Zhao 2,  Michael Hu 2,  Ann Tipps 5,  Kun Zhang 6,  Prashant Mali 7
Affiliations

Affiliations

  • 1 Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, San Diego, CA 92093, USA.
  • 2 Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
  • 3 Department of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA.
  • 4 Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, CA 92093, USA.
  • 5 School of Medicine, University of California, San Diego, San Diego, CA 92103, USA.
  • 6 Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, San Diego, CA 92093, USA. Electronic address: kzhang@bioeng.ucsd.edu.
  • 7 Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, San Diego, CA 92093, USA. Electronic address: pmali@ucsd.edu.
PMID: 33152263 DOI: 10.1016/j.cell.2020.10.018
Abstract

We propose that the teratoma, a recognized standard for validating pluripotency in stem cells, could be a promising platform for studying human developmental processes. Performing single-cell RNA Sequencing (RNA-seq) of 179,632 cells across 23 teratomas from 4 cell lines, we found that teratomas reproducibly contain approximately 20 cell types across all 3 germ layers, that inter-teratoma cell type heterogeneity is comparable with Organoid systems, and teratoma gut and brain cell types correspond well to similar fetal cell types. Furthermore, cellular barcoding confirmed that injected stem cells robustly engraft and contribute to all lineages. Using pooled CRISPR-Cas9 knockout screens, we showed that teratomas can enable simultaneous assaying of the effects of genetic perturbations across all germ layers. Additionally, we demonstrated that teratomas can be sculpted molecularly via MicroRNA (miRNA)-regulated suicide gene expression to enrich for specific tissues. Taken together, teratomas are a promising platform for modeling multi-lineage development, pan-tissue functional genetic screening, and tissue engineering.

Keywords

CRISPR-Cas9; barcoding; genetic circuits; genetic screens; miRNAs; model systems; multi-lineage development; single-cell RNA sequencing; teratoma; tissue engineering.

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