The transcriptional and regulatory identity of erythropoietin producing cells.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
23
01
2022
accepted:
17
03
2023
medline:
24
5
2023
pubmed:
28
4
2023
entrez:
27
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37106166
doi: 10.1038/s41591-023-02314-7
pii: 10.1038/s41591-023-02314-7
doi:
Substances chimiques
Erythropoietin
11096-26-7
RNA
63231-63-0
EPO protein, human
0
Epo protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1191-1200Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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