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Generating trunk neural crest from human pluripotent stem cells.

Miller Huang1, Matthew L Miller1, Lauren K McHenry1

  • 1Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.

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Researchers developed a new method to guide human pluripotent stem cells (PSCs) toward trunk neural crest cells (NCCs) and sympathoadrenal lineages, overcoming challenges in studying human NCC biology.

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Human Embryology

Background:

  • Neural crest cells (NCCs) are versatile stem cells crucial for development, but their study in humans is limited by ethical and practical challenges.
  • Existing methods for differentiating human pluripotent stem cells (PSCs) into NCCs often yield cranial-type NCCs, limiting research into posterior NCC derivatives.
  • Differences between human and non-human NCCs highlight the need for direct study of human NCCs.

Purpose of the Study:

  • To establish a robust protocol for differentiating human PSCs into trunk NCCs and subsequent sympathoadrenal lineages.
  • To investigate the roles of retinoic acid and bone morphogenetic proteins (BMPs) in directing human NCC differentiation.
  • To overcome the bias towards cranial NCCs in current human PSC differentiation protocols.

Main Methods:

  • Human pluripotent stem cells (PSCs) were differentiated using modified protocols.
  • Retinoic acid was added to induce posterior identity markers and HOX genes.
  • Bone morphogenetic proteins (BMPs) were subsequently used to enhance differentiation towards sympathoadrenal cells.

Main Results:

  • The protocol successfully directed human PSCs towards a posterior NCC identity, indicated by trunk-related markers and HOX gene expression.
  • Addition of BMPs significantly improved differentiation efficiency into sympathoadrenal cells.
  • The developed methodology provides a reliable system for studying human trunk NCCs and their derivatives.

Conclusions:

  • This study presents a novel method for generating human trunk NCCs and sympathoadrenal cells from PSCs.
  • Retinoic acid and BMPs are key signaling molecules in directing human PSC differentiation towards posterior NCC lineages.
  • The findings facilitate deeper investigation into human NCC biology and associated developmental processes.