Stemness

Stemness describes the collection of traits that enable a cell to behave as a stem cell. Central to stemness are self-renewal, the capacity to undergo numerous cycles of cell division while maintaining an undifferentiated state, and potency, the ability to generate multiple cell lineages or tissue types. In development and tissue homeostasis, stemness allows stem cells to replenish lost cells and contribute to organ formation.

Molecularly, stemness is associated with a transcriptional network that includes master regulators such as OCT4 (POU5F1), SOX2, and NANOG in many systems, along with tissue-specific factors. Epigenetic features such as open chromatin at stemness genes and often bivalent histone marks prime cells for differentiation. Stemness is also linked to metabolic and cell-cycle features that support long-term self-renewal.

Assessment typically relies on functional tests of self-renewal and multipotency, such as serial transplantation or colony/sphere formation assays, in addition to profiling surface markers and transcriptional signatures. Markers vary by tissue; for example, hematopoietic stem cells express CD34 and RUNX1, while neural and epithelial stem cells have distinct profiles. In cancer, subpopulations with stemness traits—cancer stem cells—are proposed to drive tumor growth, metastasis, and drug resistance.

Stemness is not an intrinsic, immutable property. It is context-dependent and influenced by the stem cell niche, signaling pathways including WNT, Notch, Hedgehog, FGF, and TGF-β, and cellular metabolism. The concept also encompasses the ability of differentiated cells to reacquire stem-like features through reprogramming or dedifferentiation, which underpins induced pluripotent stem cell technology.

Because stemness reflects a spectrum of capabilities rather than a binary state, its assessment is subject to methodological differences and biological variability. Nevertheless, understanding stemness is central to development, regenerative medicine, and oncology.