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Thyroid Stem Cell Speciation-a Major Role for PKC.

Rauf Latif1,2, Syed A Morshed1,2, Colin McCann1

  • 1Thyroid Research Unit, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Endocrinology
|April 30, 2023
PubMed
Summary
This summary is machine-generated.

Protein kinase C (PKC) activation, particularly PKCξ, drives thyroid progenitor cell development by enhancing thyroid-specific gene expression via the TAK1/NFκB pathway, distinct from the PKA pathway.

Keywords:
PKCstem cellsthyroid

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Area of Science:

  • Stem cell biology
  • Endocrinology
  • Molecular signaling

Background:

  • Thyroid follicle formation is regulated by complex instructive signals, primarily thyrotropin (TSH).
  • Understanding the specific signaling pathways involved in thyroid progenitor cell development from stem cells is crucial.

Purpose of the Study:

  • To investigate the role of protein kinase C (PKC) in thyroid progenitor cell development using a Gαq/11 biased small molecule, MSq1.
  • To elucidate the signaling pathways, including PKC and protein kinase A (PKA), that regulate key thyroid-specific genes.

Main Methods:

  • Mouse embryonic stem cells (mESCs) were differentiated and treated with TSH or MSq1, with or without PKC inhibitors.
  • Transcriptional and translational analysis of thyroid markers (NIS, TG, TSHR) and signaling molecules.
  • PKC isoform analysis and investigation of downstream pathways like TAK1/NFκB.

Main Results:

  • MSq1 potently activated Gαq/11 signaling, surpassing TSH.
  • MSq1-induced PKC activation significantly increased thyroid-specific gene expression (TG, NIS).
  • PKC inhibition, but not PKA inhibition, suppressed TG and NIS expression, highlighting PKC's dominant role.

Conclusions:

  • PKC activation is a dominant pathway in inducing thyroid hormone production, with PKCξ being the key mediator.
  • The TAK1/NFκB pathway is involved in MSq1-induced thyroid differentiation.
  • This study identifies a novel PKC-dependent mechanism for thyroid development from stem cells.