Amazing stuff! Well done! Apparently, very challenging research like a needle in the haystack and involving forensic tissue samples from house fire victims!
"... Even then, exposing the Norn cells was a significant challenge, as each one produces very small amounts. In 3,000 kidney cells that were studied, they found fewer than 40 cells actively producing EPO. ..."
"... scientists ... have identified a rare subset of kidney cells that are the main producers of EPO in the human body. The researchers named them Norn cells, after the mythological Norse creatures believed to spin the threads of fate. The discovery has transformative potential for patients with anemia. ...
In earlier research, ... team had created transgenic mice in which EPO-producing cells permanently turned a glowing red, making it possible to close in on the area in the kidneys in which these cells reside. ...
exposing EPO-producing cells proved to be a significant challenge. “These cells have no known markers, produce very little EPO in normal oxygen conditions and exhibit irregular EPO production during hypoxia,” ...
After numerous attempts, the researchers managed to identify fewer than 40 cells actively producing EPO, out of about 3,000 red-glowing kidney cells. This was enough for them to decipher – for the first time – the molecular fingerprint of EPO-producing cells and show that these cells maintain their identity in kidney samples even under normal oxygen levels. ...
the team contacted a forensic scientist in Germany, who donated tissue samples from the kidneys of house fire victims who had died from carbon monoxide poisoning. These samples allowed the scientists to identify the long-sought EPO-producing Norn cells in humans, and to show that they are the same cells as those they had earlier identified in mice. ..."
In earlier research, ... team had created transgenic mice in which EPO-producing cells permanently turned a glowing red, making it possible to close in on the area in the kidneys in which these cells reside. ...
exposing EPO-producing cells proved to be a significant challenge. “These cells have no known markers, produce very little EPO in normal oxygen conditions and exhibit irregular EPO production during hypoxia,” ...
After numerous attempts, the researchers managed to identify fewer than 40 cells actively producing EPO, out of about 3,000 red-glowing kidney cells. This was enough for them to decipher – for the first time – the molecular fingerprint of EPO-producing cells and show that these cells maintain their identity in kidney samples even under normal oxygen levels. ...
the team contacted a forensic scientist in Germany, who donated tissue samples from the kidneys of house fire victims who had died from carbon monoxide poisoning. These samples allowed the scientists to identify the long-sought EPO-producing Norn cells in humans, and to show that they are the same cells as those they had earlier identified in mice. ..."
From the abstract:
"Erythropoietin (Epo) is the master regulator of erythropoiesis and oxygen homeostasis. Despite its physiological importance, the molecular and genomic contexts of the cells responsible for renal Epo production remain unclear, limiting more-effective therapies for anemia. Here, we performed single-cell RNA and transposase-accessible chromatin (ATAC) sequencing of an Epo reporter mouse to molecularly identify Epo-producing cells under hypoxic conditions. Our data indicate that a distinct population of kidney stroma, which we term Norn cells, is the major source of endocrine Epo production in mice. We use these datasets to identify the markers, signaling pathways and transcriptional circuits characteristic of Norn cells. Using single-cell RNA sequencing and RNA in situ hybridization in human kidney tissues, we further provide evidence that this cell population is conserved in humans. These preliminary findings open new avenues to functionally dissect EPO gene regulation in health and disease and may serve as groundwork to improve erythropoiesis-stimulating therapies."
Decades-Old Mystery of Red Blood Cell Production Finally Solved Identifying the cells producing the hormone EPO may lead to the development of new therapies for treating anemia resulting from kidney disease and other conditions
Kidney tissue of a person who died of smoke inhalation (carbon monoxide poisoning), viewed under a microscope. Markers reveal the kidney cell nuclei (blue), EPO (green) and fibroblasts (purple). On the right: The combination of different markers points to EPO-producing Norn cells (white arrows) that were discovered in the study
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