Loading...
Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells
Thej, Charan Roy, Rajika Cheng, Zhongjian Srikanth Garikipati, Venkata Naga Truongcao, May M. Joladarashi, Darukeshwara Mallaredy, Vandana Cimini, Maria Gonzalez, Carolina Magadum, Ajit
Thej, Charan
Roy, Rajika
Cheng, Zhongjian
Srikanth Garikipati, Venkata Naga
Truongcao, May M.
Joladarashi, Darukeshwara
Mallaredy, Vandana
Cimini, Maria
Gonzalez, Carolina
Magadum, Ajit
Citations
Altmetric:
Genre
Journal article
Date
2024-04-29
Advisor
Committee member
Department
Cardiovascular Sciences
Subject
Permanent link to this record
Collections
Files
Research Projects
Organizational Units
Journal Issue
DOI
https://doi.org/10.1038/s41536-024-00362-2
Abstract
Historically, a lower incidence of cardiovascular diseases (CVD) and related deaths in women as
compared with men of the same age has been attributed to female sex hormones, particularly estrogen
and its receptors. Autologous bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy
overwhelmingly included male patients. However, meta-analysis data from these trials suggest a
better functional outcome in postmenopausal women as compared with aged-matched men.
Mechanisms governing sex-specific cardiac reparative activity in BMSCs, with and without the
influence of sex hormones, remain unexplored. To discover these mechanisms, Male (M), female (F),
and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and
epigenetic analyses followed by in vivo functional assessments of cardiac repair. F-EPCs and OVX
EPCs show a lower inflammatory profile and promote enhanced cardiac reparative activity after intracardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing
revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at
transcription start sites of key angiogenic and proinflammatory genes in M-EPCs compared with
F-EPCs and OVX-EPCs. Our study unveiled that functional sex differences in EPCs are, in part,
mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3,
orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research
highlights the importance of considering the sex of donor cells for progenitor-based tissue repair.
Description
Citation
Thej, C., Roy, R., Cheng, Z. et al. Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells. npj Regen Med 9, 17 (2024). https://doi.org/10.1038/s41536-024-00362-2
Citation to related work
Springer Science and Business Media
Has part
NPJ Regenerative Medicine, Vol. 9, Iss. 1
ADA compliance
Embedded videos
License
Attribution CC BY