Chapter 37 - The Vasculome provides a body-wide cellular positioning system and functional barometer. The “Vasculature asCommonCoordinateFrame (VCCF)” concept

Abstract

We are standing at the beginning of a new era of biology and medicine: many different technological innovations have converged to produce an unprecedented amount and diversity of detailed data about the human body. The biggest challenges we face are related to our current ability to organize and interpret this enormous amount of multidimensional data to extract biological and medical knowledge. For instance, many recent efforts to develop accurate single cell–level resolution maps of human tissues and organs have highlighted the essential need to identify a common coordinate framework (CCF) for the human body that could be widely understood and adopted to accurately assign spatial locations for individual cells and the high content, multidimensional information associated with each of them. This goal is yet to be reached, but progress has been made thanks to many researchers highlighting essential challenges and coming together to prioritize the key desirable characteristics for a human body CCF. Briefly, this CCF would need to work across the several human body scales, be applicable to all (or most) tissues, be able to account for donor differences (e.g., size, shape, sex), and to be useful and acceptable across specialty domains. In direct response to these requirements, I have proposed the “Vasculature as CCF” concept and presented in diverse contexts how based on its natural structural and functional design the vasculature could meet the widely accepted design requirements for a human body CCF. The “Vasculature as CCF” concept is based on the Vasculome's body of knowledge about the unified nature of the vasculature and its essential importance to the survival and function of every cell in the human body. An even more elegant CCF solution has emerged through the constant updating of this knowledge about vasculature with the latest discoveries, and by working to offer practical suggestions about how the “Vasculature for CCF” concept may be applied. Specifically, recent single-cell analysis reports have shown that the endothelial cells (ECs), which form the continuous lining of the entire vasculature, provide their precise positional information within the vasculature, organ, and tissue, information that can be thought of as a molecular EC zip code. ECs molecular signatures have been also shown to be sensitive to changes affecting their local tissue context, as well as to systemic conditions. I am suggesting that ECs may not only be sufficient as a CCF, providing a body-wide positional system for other cells, but also well suited as a functional barometer for various organs' functional tissue units (FTUs), tissue neighborhoods, and body-wide health status. Further development of analytical and computational approaches, including machine learning and artificial intelligence, is needed to pursue and refine this concept, but it is clear that knowledge about the vasculature—effectively the Vasculome—stands ready to provide key support for the next phase of precision biology, and a fundamental basis for precision medicine.