miR-302 and miR-367: Key Players in Pluripotency and Reprogramming
miR-302 and miR-367 are microRNAs (miRNAs) that play a crucial role in maintaining pluripotency and enhancing somatic cell reprogramming into induced pluripotent stem cells (iPSCs). They are part of the miR-302/367 cluster, which is highly expressed in embryonic stem cells (ESCs) and is critical for their self-renewal and reprogramming potential.
- What Are miR-302 and miR-367?
miR-302 is a family of microRNAs (miR-302a, miR-302b, miR-302c, miR-302d) that share a common seed sequence.
miR-367 is a single microRNA that works alongside miR-302 to reinforce pluripotency.
They are encoded by the miR-302/367 cluster, which is transcriptionally activated by pluripotency factors such as OCT4, SOX2, and NANOG.
- Functions of miR-302 and miR-367 in Reprogramming & Pluripotency
A. Enhancing Somatic Cell Reprogramming
Promotes iPSC generation: Overexpression of the miR-302/367 cluster can reprogram somatic cells into iPSCs without requiring c-MYC and KLF4, reducing genomic instability.
Epigenetic remodeling: These miRNAs help reset the somatic epigenetic state and promote a pluripotent chromatin landscape.
B. Cell Cycle Regulation for Self-Renewal
miR-302/367 suppresses cyclin-dependent kinase inhibitors (CDKIs) (e.g., p21, p57), promoting rapid cell cycle progression, which is characteristic of stem cells.
This leads to shortened G1 phase, making cells more prone to reprogramming and pluripotency maintenance.
C. Inhibiting Differentiation & Maintaining Pluripotency
miR-302/367 inhibits differentiation-inducing genes, reinforcing a stem-like state.
Suppresses TGF-β signaling, which promotes differentiation, thereby keeping cells in a self-renewing state.
D. Reducing DNA Damage & Apoptosis
miR-302 enhances genome stability by downregulating genes involved in DNA damage responses.
Helps protect iPSCs from oxidative stress and apoptosis.
- Comparison to Traditional Yamanaka Factors (OCT4, SOX2, KLF4, c-MYC)
The miR-302/367 cluster can reprogram cells to iPSCs more efficiently than the traditional Yamanaka factors, particularly without c-MYC, reducing tumorigenic risks.
Faster and more homogeneous reprogramming with miR-302/367 compared to traditional methods.
- Therapeutic & Research Applications
Safer iPSC Generation: miR-302/367 can replace viral-based transcription factor delivery, reducing the risk of oncogene activation.
Cancer Therapy: Since miR-302/367 inhibits tumor-promoting pathways, it is being explored as a potential anti-cancer therapy.
Neurodevelopmental & Cardiac Repair: These miRNAs have potential for reprogramming cells into neurons and cardiomyocytes for regenerative medicine.
Conclusion
miR-302 and miR-367 are powerful tools for cell reprogramming, pluripotency maintenance, and regenerative medicine. Their ability to induce iPSC formation without oncogenic risks makes them an attractive alternative to traditional Yamanaka factors.
Would you like a breakdown of experimental protocols for using miR-302/367 in iPSC generation?
