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

TL;DR

This paper proposes the concept of Heritable Nongenetic Information (HNI), a heritable form of biological information beyond DNA that governs tissue structure, development, regeneration, and tumor architecture, emphasizing its quasi-epigenetic nature.

Contribution

The paper introduces HNI as a broader term for spatial codes in biology, independent of DNA modifications, and highlights its role in tissue organization and inheritance.

Findings

HNI is heritable and influences tissue architecture.

Tissue spatial codes are distinct from traditional epigenetic mechanisms.

Pre-existing physiological information is necessary for tissue structure formation.

Abstract

Numerous studies of the tumor microenvironment, interspecies xenografting, and limb regeneration suggest the existence of a Tissue Spatial Code (TSC) that controls tissue structure in a quasi-epigenetic fashion. The term 'epigenetic' is an inadequate label for the concept that encompasses the TSC, because this information does not act upon DNA or chromatin via post-translational modifications (i.e. DNA methylation, histone acetylation). A broader term is needed to capture the diversity of three-dimensional (3D) spatial codes in biology. 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 have disappeared during evolution. Another reason for the heritability of HNI is that the spatial information observed in tissues is not reducible to the laws of physics, meaning structures like epithelial tubes or neural circuits do not spontaneously form in an aqueous solution; pre-existing physiological information in the microenvironment is necessary. In summary, HNI is defined as: heritable, instructional information that affects molecular-, cellular-, tissue-, or organ-level function without having to post-translationally modify DNA or chromatin in order to be inherited.