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Numerous studies of the tumor microenvironment, interspecies xenografting,and limb regeneration suggest the existence of a Tissue Spatial Code (TSC) thatcontrols tissue structure in a quasi-epigenetic fashion. The term 'epigenetic'is an inadequate label for the concept that encompasses the TSC, because thisinformation does not act upon DNA or chromatin via post-translationalmodifications (i.e. DNA methylation, histone acetylation). A broader term isneeded to capture the diversity of three-dimensional (3D) spatial codes inbiology. One such term is Heritable Nongenetic Information (HNI, pronounced'honey'), which encompasses the TSC. The term 'heritable' is appropriate,because this information is passed onto offspring, otherwise it would havedisappeared during evolution. Another reason for the heritability of HNI isthat the spatial information observed in tissues is not reducible to the lawsof physics, meaning structures like epithelial tubes or neural circuits do notspontaneously form in an aqueous solution; pre-existing physiologicalinformation in the microenvironment is necessary. In summary, HNI is definedas: heritable, instructional information that affects molecular-, cellular-,tissue-, or organ-level function without having to post-translationally modifyDNA or chromatin in order to be inherited.

Heritable Nongenetic Information That is Independent of DNA and That Governs Organismal Development, Tissue Regeneration, and Tumor Architecture