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

Rihao Qu, Khusali Gupta, Danni Dong, Yiqun Jiang, Boris Landa, Charles Saez, Gwendolyn Strickland, Jonathan Levinsohn, Pei lun Weng, M. Mark Taketo, Yuval Kluger, Peggy Myung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Organ formation requires integrating signals to coordinate proliferation, specify cell fates, and shape tissue. Tracing these events and signals remains a challenge, as intermediate states across many critical transitions are unresolvable over real time and space. Here, we designed a unique computational approach to decompose a non-linear differentiation process into key components to resolve the signals and cell behaviors that drive a rapid transition, using the hair follicle dermal condensate as a model. Combining scRNA sequencing with genetic perturbation, we reveal that proliferative Dkk1+ progenitors transiently amplify to become quiescent dermal condensate cells by the mere spatiotemporal patterning of Wnt/β-catenin and SHH signaling gradients. Together, they deterministically coordinate a rapid transition from proliferation to quiescence, cell fate specification, and morphogenesis. Moreover, genetically repatterning these gradients reproduces these events autonomously in “slow motion” across more intermediates that resolve the process. This analysis unravels two morphogen gradients that intersect to coordinate events of organogenesis.

Original languageEnglish
Pages (from-to)1053-1067.e5
JournalDevelopmental Cell
Issue number8
StatePublished - 25 Apr 2022
Externally publishedYes


  • Wnt
  • dermal condensate
  • dermis
  • development
  • hair follicle
  • morphogen
  • niche
  • single-cell RNA-seq
  • sonic hedgehog


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