Boster Pathways-> Developmental Biology & Stem Cells

ESC Pluripotency and Differentiation Signaling Pathway

Embryonic stem cell (ESC) cells have the ability to self-renew while maintaining their pluripotency.

Overview of ESC Pluripotency and Differentiation Signaling Pathway

Due to their capabilities of infinite self-renewal in vitro and the potential to develop into cell types representative of the three embryonic germ layers—mesoderm, ectoderm, and endoderm—pluripotent stem cells (PSCs) are at the heart of modern regenerative medicine. The use of induced PSCs avoids the ethical issues that come with using human embryonic stem cells while simultaneously allowing for individualized cell-based therapeutics. To fully use their regenerative potential, a thorough understanding of the molecular pathways involved in their induction from somatic cells is required. This knowledge serves two purposes: first, it allows for the efficient, dependable, and cost-effective production of high-quality induced PSCs, and second, it allows for the derivation of safe, GMP-grade transplantable donor cells. We focus on self-renewal, epigenetic control, mitochondrial bioenergetics, sub-states of pluripotency, naive ground state, naive and primed, and associated processes in this overview of the reprogramming of somatic cells into induced PSCs and associated mechanisms.

Genes expressed primarily in the inner cell mass and in the naive but not in the primed pluripotent state were discovered in a meta-analysis. These are proposed as additional biomarkers for naive PSCs.

Mechanism of ESC Pluripotency and Differentiation Signaling Pathway

Pluripotency and the ability to self-renew are two distinguishing properties of embryonic stem cells (ESCs). A number of cell signaling pathways regulate these traits, which allow ESCs to grow into any cell type in the adult body and divide continuously in the undifferentiated state. TGF-, which signals through Smad2/3/4, and FGFR, which activates the MAPK and Akt pathways, are the most important signaling pathways involved in pluripotency and self-renewal in human ESCs (hESCs). Although a non-canonical mechanism involving a balance between the transcriptional activator TCF1 and the repressor TCF3 may promote pluripotency, the Wnt pathway does so. The pluripotent state is supported by signaling across these pathways, which is dependent on three major transcription factors: Oct-4, Sox2, and Nanog. These transcription factors regulate their own expression, repress genes involved in differentiation, and function as hESC markers in addition to activating ESC-specific genes. The cell surface glycolipid SSEA3/4 and the glycoproteins TRA-1-60 and TRA-1-81 are also utilized to identify hESCs. In vitro, hESCs can be coaxed into endoderm, mesoderm, or ectoderm derivatives, as well as primordial germ cell-like cells.

The BMP pathway, which uses Smad1/5/9 to promote differentiation by inhibiting Nanog expression while activating differentiation-specific genes, is one of the primary signaling pathways involved in this process. Through the notch intracellular domain, Notch also plays a role in differentiation (NICD). Cells from each primary germ layer continue to differentiate along lineage-specific pathways as differentiation progresses.