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The transcriptional and regulatory identity of erythropoietin producing cells. 2023
Bjørt K Kragesteen, and
Amir Giladi, and
Eyal David, and
Shahar Halevi, and
Laufey Geirsdóttir, and
Olga M Lempke, and
Baoguo Li, and
Andreas M Bapst, and
Ken Xie, and
Yonatan Katzenelenbogen, and
Sophie L Dahl, and
Fadi Sheban, and
Anna Gurevich-Shapiro, and
Mor Zada, and
Truong San Phan, and
Roberto Avellino, and
Shuang-Yin Wang, and
Oren Barboy, and
Shir Shlomi-Loubaton, and
Sandra Winning, and
Philipp P Markwerth, and
Snir Dekalo, and
Hadas Keren-Shaul, and
Merav Kedmi, and
Martin Sikora, and
Joachim Fandrey, and
Thorfinn S Korneliussen, and
Josef T Prchal, and
Barak Rosenzweig, and
Vladimir Yutkin, and
Fernando Racimo, and
Eske Willerslev, and
Chamutal Gur, and
Roland H Wenger, and
Ido Amit
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. bjort.kragesteen@weizmann.ac.il.
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.
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