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Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men
Christa Broholm1, Rasmus Ribel-Madsen1,2, Line Hjort1,2,3
1Department of Endocrinology, Diabetes and Bone-metabolic Research Unit, Copenhagen, Denmark.
Endocrine Research
|October 1, 2019
Summary
Low birth weight (LBW) in men is linked to epigenetic changes in muscle stem cells, impairing muscle development and increasing type 2 diabetes risk. These changes include altered DNA methylation and reduced expression of HDAC7 and FYN genes.
Area of Science:
- Epigenetics
- Metabolic Health
- Developmental Biology
Background:
- Low birth weight (LBW) is a known risk factor for muscle insulin resistance and type 2 diabetes (T2D).
- Epigenetic mechanisms, influenced by the intrauterine environment, are hypothesized to mediate these risks.
- Early alterations in muscle progenitor cells may underlie insulin resistance in LBW individuals.
Purpose of the Study:
- To investigate early epigenomic and transcriptomic differences in muscle progenitor cells from individuals born with LBW.
- To determine if these alterations contribute to impaired muscle development and predisposition to T2D.
Main Methods:
- Muscle progenitor cells were isolated from term-born adult men with LBW and normal birth weight (NBW) controls.
- Cells were cultured and differentiated into myotubes, with DNA and RNA harvested pre- and post-differentiation.
- Genome-wide DNA methylation and RNA expression analyses were performed.
Main Results:
- Significant differential DNA methylation was observed in myoblasts from LBW compared to NBW men.
- LBW men showed decreased myotube gene expression of FYN and HDAC7.
- Silencing of FYN and HDAC7 correlated with impaired myotube formation and reduced muscle glucose uptake (for HDAC7).
Conclusions:
- Distinct DNA methylation and transcriptional changes occur in immature muscle stem cells of LBW individuals.
- Downregulation of HDAC7 and FYN in these cells is linked to impaired muscle development.
- These early cellular changes may predispose LBW individuals to type 2 diabetes.
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