The transcriptional and regulatory identity of erythropoietin producing cells

Research output: Contribution to journalJournal articleResearchpeer-review

  • Bjørt K. Kragesteen
  • Amir Giladi
  • Eyal David
  • Shahar Halevi
  • Laufey Geirsdóttir
  • Olga M. Lempke
  • Baoguo Li
  • Andreas M. Bapst
  • Ken Xie
  • Yonatan Katzenelenbogen
  • Sophie L. Dahl
  • Fadi Sheban
  • Anna Gurevich-Shapiro
  • Mor Zada
  • Truong San Phan
  • Roberto Avellino
  • Shuang-Yin Wang
  • Oren Barboy
  • Shir Shlomi-Loubaton
  • Sandra Winning
  • Philipp P. Markwerth
  • Snir Dekalo
  • Hadas Keren-Shaul
  • Merav Kedmi
  • Joachim Fandrey
  • Josef T. Prchal
  • Barak Rosenzweig
  • Vladimir Yutkin
  • Chamutal Gur
  • Roland H. Wenger
  • Ido Amit

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.

Original languageEnglish
JournalNature Medicine
Issue number5
Pages (from-to)1191-1200
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

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