School of Biological Science, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
Cell Death Dis. 2018 Sep 11;9(9):914. doi: 10.1038/s41419-018-0993-z.
Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signaling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.
单核细胞的分化需要它们从血液迁移到组织中，因此伴随着理化微环境的改变。虽然已知微环境的生化组成如何诱导分化的机制，但物理微环境的流变体到凝胶体的转变尚不清楚。单核细胞保持非附着状态以防止分化。我们确定，无论化学成分如何，3D 凝胶样微环境都会诱导粘附-MAPK-NF-κβ 激活的正反馈环，从而促进分化。在 2D 流体样微环境中，仅通过相同的正反馈信号即可通过粘附诱导分化。在流体样微环境中进行化学诱导剂处理会通过短暂的 p-MAPK 脉冲增加单核细胞粘附的倾向。随后的粘附引发分化，这表明在 2D/3D 微环境中，粘附既是必要条件，也是诱导分化的充分条件。由于 MAPK 和 NF-κβ 是多种信号通路的关键分子，我们假设化学惰性的 3D 凝胶样微环境也会影响其他细胞功能。
