A spatiotemporal and machine-learning platform facilitates the manufacturing of hPSC-derived esophageal mucosa.

Journal: Developmental cell
PMID: 39798574

Abstract

Human pluripotent stem cell-derived tissue engineering offers great promise for designer cell-based personalized therapeutics, but harnessing such potential requires a deeper understanding of tissue-level interactions. We previously developed a cell replacement manufacturing method for ectoderm-derived skin epithelium. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium despite possessing a similar stratified epithelial structure. Here, we employ single-cell and spatial technologies to generate a spatiotemporal multi-omics cell census for human esophageal development. We identify the cellular diversity, dynamics, and signal communications for the developing esophageal epithelium and stroma. Using Manatee, a machine-learning algorithm, we prioritize the combinations of candidate human developmental signals for in vitro derivation of esophageal basal cells. Functional validation of Manatee predictions leads to a clinically compatible system for manufacturing human esophageal mucosa.

Authors

  • Ying Yang
    Department of Endocrinology, The Affiliated Hospital of Yunnan University, Kunming, China.
  • Carmel Grace McCullough
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA.
  • Lucas Seninge
    Department of Biomolecular Engineering and Genomics Institute, University of California, Santa Cruz, CA, USA.
  • Lihao Guo
    Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ, USA.
  • Woo-Joo Kwon
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA.
  • Yongchun Zhang
    State Key Laboratory of Microbial Metabolism & Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • Nancy Yanzhe Li
  • Sadhana Gaddam
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA.
  • Cory Pan
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA.
  • Hanson Zhen
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA.
  • Jessica Torkelson
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA.
  • Ian A Glass
    Birth Defect Research Laboratory Department of Pediatrics, University of Washington, Seattle, WA, USA.
  • Gregory W Charville
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Jianwen Que
    Columbia Center for Human Development, Department of Medicine, Columbia University Medical Center, New York, NY, USA. jq2240@cumc.columbia.edu.
  • Joshua M Stuart
    University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Hongxu Ding
    Department of Biomolecular Engineering and Genomics Institute, University of California, Santa Cruz, CA, USA. hding16@ucsc.edu.
  • Anthony E Oro
    Program in Epithelial Biology and Center for Definitive and Curative Medicine, Stanford University, Stanford, CA, USA. Electronic address: oro@stanford.edu.

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