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

First Author  Qu R Year  2022
Journal  Dev Cell Volume  57
Issue  8 Pages  1053-1067.e5
PubMed ID  35421372 Mgi Jnum  J:324528
Mgi Id  MGI:7279212 Doi  10.1016/j.devcel.2022.03.011
Citation  Qu R, et al. (2022) Decomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients. Dev Cell 57(8):1053-1067.e5
abstractText  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/beta-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.
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