Identifying niche‐mediated regulatory factors of stem cell phenotypic state: a systems biology approach

Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell–niche interactions. Here, we propose a systems biology view that considers stem cell–niche interactions as a many‐body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell‐based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering.