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Updated: Jul 11, 2025

Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
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Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development

Miao Cui1, Svetlana Bezprozvannaya2, Tian Hao3

  • 1Department of Cardiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Developmental Cell
|November 16, 2023
PubMed

Insights

The transcription factor NFYa is crucial for prenatal heart development, regulating cardiomyocyte metabolism and proliferation. Its loss impairs mitochondrial function, leading to cardiac defects and embryonic lethality in mice.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • Cardiomyocytes are highly metabolic cells essential for heart function.
  • While cardiomyocytes proliferate during fetal development, this capacity is lost in adulthood.
  • Mechanisms coordinating cardiomyocyte metabolism and proliferation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the transcription factor NFYa in mouse heart development.
  • To elucidate how NFYa regulates cardiomyocyte metabolism and proliferation during prenatal growth.

Main Methods:

  • Spatial and single-cell transcriptome analyses were employed in NFYa-deleted mouse hearts.
  • Cardiomyocyte composition, proliferation, and mitochondrial metabolism were assessed.

Main Results:

  • Loss of NFYa altered cardiomyocyte composition, decreasing regenerative cells and increasing mature cells.
  • NFYa-deficient cardiomyocytes showed reduced proliferation and impaired mitochondrial metabolism.
  • NFYa deletion resulted in cardiac growth defects and embryonic lethality.

Conclusions:

  • NFYa plays a critical role in prenatal cardiac growth by coordinating cardiomyocyte metabolism and proliferation.
  • NFYa, with cofactor SP2, transcriptionally regulates genes linking metabolism and proliferation.
  • Mitochondrial metabolism is highlighted as vital for heart development and regeneration.
Keywords:
cardiac metabolismcardiomyocyte proliferationheart developmentnuclear transcription factor Y

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