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Decomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients.

Rihao Qu1, Khusali Gupta2, Danni Dong3

  • 1Computational Biology & Bioinformatics Program, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale University, New Haven, CT 06520, USA; Department of Immunobiology, Yale University, New Haven, CT 06520, USA.

Developmental Cell
|April 14, 2022
PubMed
Summary

Researchers developed a computational method to understand organ formation. This study reveals how two signaling gradients control hair follicle development by coordinating cell proliferation, fate, and shape.

Keywords:
Wntdermal condensatedermisdevelopmenthair folliclemorphogennichesingle-cell RNA-seqsonic hedgehog

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Area of Science:

  • Developmental Biology
  • Computational Biology
  • Genetics

Background:

  • Organ formation involves complex signaling pathways that regulate cell behavior.
  • Understanding the real-time dynamics of these processes is challenging due to unresolvable intermediate states.

Purpose of the Study:

  • To develop a computational approach to dissect non-linear differentiation processes.
  • To identify the specific signals and cell behaviors driving rapid transitions in organogenesis.
  • To model the hair follicle dermal condensate as a system for studying organ formation.

Main Methods:

  • Utilized a novel computational strategy to analyze differentiation.
  • Employed single-cell RNA sequencing (scRNA-seq) and genetic perturbations.
  • Modeled spatiotemporal signaling gradients (Wnt/β-catenin and SHH).

Main Results:

  • Identified proliferative Dkk1+ progenitors transitioning to quiescent dermal condensate cells.
  • Demonstrated that Wnt/β-catenin and SHH signaling gradients deterministically control proliferation, quiescence, cell fate, and morphogenesis.
  • Showed that genetic manipulation of these gradients recapitulates developmental events in a "slow-motion" manner, revealing intermediate states.

Conclusions:

  • Two intersecting morphogen gradients are crucial for coordinating organogenesis events.
  • The study provides a framework for resolving complex developmental processes computationally.
  • This work elucidates the precise roles of signaling gradients in hair follicle development.