New molecular atlas reveals cell 'neighborhoods'
Tissues and organs function — or fail — thanks to the interactions of trillions of cells arranged in intricate patterns.
So, to help develop an open reference of cells in the human body, the NIH established the Human BioMolecular Atlas Program (HuBMAP).
Now, several papers published in the journal Nature and across Nature Portfolio journals reveal the fruits of five years of effort by 500 contributors across 40 institutions, including new discoveries regarding the human intestine, kidneys and maternal-fetal interface.
“A big part of this whole effort has been to build a framework, tools and resources for scaling to the entire body so we can make a consistent map across all the investigators who are working with us,” said Michael Snyder of Stanford University, senior author on a paper describing the human intestine at single-cell resolution.
Genetic and genomic analysis can sort cells into their functions, like parts of a car engine. But really understanding them requires seeing where they go and how they work together.
By using molecular tags, barcodes and imaging to nail down cellular addresses, researchers found specialized cells in the intestine and kidneys are organized into distinct zones, some complete with immune system “neighborhood watches.”
“Cells are not randomly distributed; you don't just throw them together and hope they work,” said Snyder. “They're actually organized into something we call neighborhoods — discrete domains of groups of cells — and they actually can vary across the intestine. And that probably represents different functions.”
He said the master planned communities don’t end there.
“The neighborhoods themselves can be grouped into also bigger structures — communities, we like to call them — so you actually have a hierarchical organization,” he said.
In addition to areas zoned for immune cells, kidneys also include neighborhoods of stromal cells, which secrete collagen and can cause fibrosis by creating scar tissue in response to certain diseases or chronic conditions. Sanjay Jain of Washington University in St. Louis, senior author of a paper describing cell states in the human kidney, saw a pattern in the layout of stromal neighborhoods and functional cells.
“In a healthy state, they have a unique arrangement; and when the kidney is damaged, then they have a completely different arrangement of these neighborhoods and the genes that are responsible,” he said. “And we found that some of these genes actually are related with worsening of kidney function in human patients that have been followed over five years.”
Researchers also figured out how a pregnant mother’s body maintains a peaceful neutral zone at the junction between the uterus and the genetically distinct placenta.
“The way the placenta attaches to the endometrium is critically important to be able to really understand this at a more granular level so that we can see how the maternal immune system adapts to be able to tolerate the fetus,” said Michael Angelo, senior author on a paper describing the maternal–fetal interface, where placenta and maternal cells coexist. “But the other thing that's really crucial is that this changes over time”
Much more research needs to be done, both to map other vital organs and tissues, and to test current findings. But the results could revolutionize medical and cellular sciences.
Katy Börner of Indiana University, co-author on an antibody paper in the series, shared her vision of the target.
“I think ultimately what we would like to have is a common coordinate framework, like a latitude and longitude system, but for the healthy human body,” she said.