HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells.
Huixin Guo1, Chengwen Hang2,3,4,5, Bowen Lin2,3,4,5
1Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Stem Cell Research & Therapy
|February 5, 2024
Summary
Transcription factors HAND1 and HAND2 are crucial for heart development. Their deficiency leads to specific cardiac defects, impacting lineage commitment and differentiation into various cardiomyocyte subtypes.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Cardiovascular Research
Background:
- Transcription factors HAND1 and HAND2 (HAND1/2) are vital for cardiac organogenesis.
- Dysregulation of HAND1/2 causes severe cardiac defects, but their role in human early cardiac lineage commitment remains unclear.
Purpose of the Study:
- To elucidate the specific and redundant functions of HAND1/2 in human early cardiac lineage commitment and differentiation.
- To investigate the underlying mechanisms of HAND1/2 in regulating cardiomyocyte subtype development.
Main Methods:
- Established HAND1 and HAND2 single and double knockout human embryonic stem cell (hESC) lines.
- Utilized flow cytometry, qPCR, western blot, immunofluorescence, and electrophysiology to analyze cardiomyocyte differentiation and function.
- Performed RNA sequencing and ChIP sequencing to identify HAND1/2 target genes.
Main Results:
- HAND1/2 deficiency delayed cardiac differentiation onset and promoted a shift towards second heart field progenitors.
- HAND1 knockout increased atrial and outflow tract cardiomyocyte markers, while HAND2 knockout reduced atrial markers.
- TBX5 was identified as a downstream target of HAND1/2, and its overexpression partially rescued differentiation defects.
Conclusions:
- HAND1/2 exhibit specific and redundant roles in cardiac lineage commitment and differentiation.
- Findings offer insights into congenital heart diseases linked to HAND1/2 deficiency and potential therapeutic avenues.
