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A Stem Cell Surge During Thyroid Regeneration.

Risheng Ma1, Syed A Morshed1, Rauf Latif1

  • 1Thyroid Research Unit, Department of Medicine, The Icahn School of Medicine at Mount Sinai and the James J. Peters VA Medical Center, New York, NY, United States.

Frontiers in Endocrinology
|February 8, 2021
PubMed
Summary
This summary is machine-generated.

Thyroid regeneration involves adult stem cells. A new mouse model shows that diphtheria toxin (DT) induces thyroid damage, mobilizing stem and progenitor cells for rapid repair and restoration of thyroid function.

Keywords:
ROSA26iDTR miceTPOCreER2 miceregenerationstem cellsthyroid

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Area of Science:

  • Endocrinology
  • Stem Cell Biology
  • Regenerative Medicine

Background:

  • Resident adult stem cells in tissues, including the thyroid, are crucial for regeneration and repair post-injury.
  • The precise mechanisms governing thyroid regeneration and the roles of thyroid stem and progenitor cells remain incompletely understood.

Purpose of the Study:

  • To investigate the mechanisms of thyroid regeneration using a novel mouse injury model.
  • To elucidate the involvement of adult stem and progenitor cells in thyroid repair after injury.

Main Methods:

  • Development of a diphtheria toxin (DT)-inducible mouse model (TPOCreER2/iDTR) to selectively ablate thyroid cells expressing thyrotropin-releasing hormone (TRH).
  • Assessment of thyroid damage, serum hormone levels (T4, TSH), gene expression, and cell fate following DT administration and subsequent withdrawal.
  • Identification of stem and progenitor cell markers (Oct4, Nanog, Sox2, Rex1, Ssea-1, Pax8) during the regeneration process.

Main Results:

  • DT-induced injury caused significant thyroid apoptosis, a ~50% decrease in serum T4, and a marked increase in TSH.
  • Thyroid-specific gene expression was reduced by approximately 50% post-injury.
  • Following DT cessation, rapid thyroid recovery occurred over 4 weeks, characterized by a surge in stem cell marker expression and the presence of stem and progenitor cells around new follicles.
  • Thyroid function was sequentially restored after the regenerative period.

Conclusions:

  • A novel DT-inducible mouse model effectively facilitates the study of resident adult stem cell mobilization in thyroid repair.
  • The findings confirm the critical involvement of both stem and progenitor cells in the in vivo regeneration of the thyroid gland following severe damage.