Evidence map›Paper›PMID 35796577›Full record

ArticleThe Journal of clinical endocrinology and metabolism2022

Characterization of Aldosterone-producing Cell Cluster (APCC) at Single-cell Resolution.

Norifusa Iwahashi, Hironobu Umakoshi, Tsugio Seki, Celso E Gomez-Sanchez, Kuniaki Mukai, Makoto Suematsu, Yuta Umezawa, Mototsugu Oya, Takeo Kosaka, Masahide Seki and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Mild autonomous cortisol secretion in primary aldosteronism: the origin of cortisol.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Article
  7. Single-Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Biomedicines · 2023
    Review
  13. Hormones and Aging: An Endocrine Society Scientific Statement.The Journal of clinical endocrinology and metabolism · 2023
    Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Norifusa IwahashiDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.ORCID 0000-0001-9881-9126
Hironobu UmakoshiDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Tsugio SekiDepartment of Medical Education, School of Medicine, California University of Science and Medicine, Colton, CA 92324, USA.
Celso E Gomez-SanchezDepartment of Pharmacology and Toxicology and Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Kuniaki MukaiMedical Education Center, Keio University School of Medicine, Tokyo 160-8582, Japan.
Makoto SuematsuDepartment of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Yuta UmezawaDepartment of Uro-Oncology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan.
Mototsugu OyaDepartment of Urology, Keio University School of Medicine Tokyo 160-8582, Japan.
Takeo KosakaDepartment of Urology, Keio University School of Medicine Tokyo 160-8582, Japan.
Masahide SekiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, Japan.ORCID 0000-0001-6091-8698
Yutaka SuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, Japan.
Yutaka HoriuchiDepartment of Microbiology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
Yoshihiro OgawaDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.ORCID 0000-0002-0834-2836
Koshiro NishimotoDepartment of Uro-Oncology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan.ORCID 0000-0002-3952-5643
Keio University · JPKyushu University · JPSaitama Medical University · JPThe University of Tokyo · JPUniversity of Mississippi Medical Center · US

Funding

Tracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI MASON, SARAH · 2016 to 2025
$38.2M
Adrenal cell ATP1A1 mutations and mechanisms of aldosterone biosynthesisR01HL144847 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI GOMEZ-SANCHEZ, CELSO ENRIQUE · 2019 to 2022
$1.3M
NHLBI NIH HHS R01 HL144847NIGMS NIH HHS U54 GM115428
6 · The paper itself

Abstract

contextThe adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters (APCCs) that strongly express aldosterone synthase (CYP11B2) are frequently found in adult adrenals and harbor somatic mutations that are also detected in aldosterone-producing adenomas (APAs). Primary aldosteronism is mainly caused by APAs or idiopathic hyperaldosteronism (IHA). We presume that APCCs are causing IHA and are precursors of APAs. However, the gene expression characteristics and especially the development of APCCs are not well understood.

objectiveThis study aimed to analyze the transcriptome of APCCs at single-cell resolution and infer the developmental trajectory.

methodsSingle-cell RNA sequencing (scRNA-seq) of 2 adult adrenals was performed.

resultsImmunohistochemical analyses confirmed the 2 adrenals had APCCs. scRNA-seq data of 2928 adrenal cells were obtained and 1765 adrenocortical cells were identified based on unsupervised clustering and the marker gene expression. The adrenocortical cells were divided into 6 clusters, of which 3 clusters (923 cells) were composed of APCC/ZG cells. By further subclustering, the APCC/ZG cells were divided into 3 clusters (clusters C1, C2, and C3), we finally identified APCC cluster (C3) and ZG cluster (C1). Cluster C2 seemed to be ZG-to-ZF transitional cells. RNA velocity analysis inferred the developmental direction from cluster ZG-cluster-C1 to APCC-cluster-C3. The scRNA-seq additionally revealed that many CYP11B2-positive cells were positive for CYP11B1 and/or CYP17A1, which were essential for cortisol but not for aldosterone production.

conclusionsOur results revealed the gene expression characteristics of APCC at single-cell resolution and show that some ZG cells remodel to APCC.

Indexed as

AdenomaAdrenal Cortex NeoplasmsHyperaldosteronismAdrenal GlandsAdultAldosteroneCytochrome P-450 CYP11B2HumansZona GlomerulosaAldosteroneCytochrome P-450 CYP11B2adrenal glandaldosterone-producing cell clustersingle-cell RNA sequencingtranscriptomic study

Identifiers

PMID35796577
PMCPMC9387688
OpenAlexW4284879376

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.