Evidence map›Paper›PMID 36413950›Full record

ArticleDevelopmental cell2022

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells.

Yuka Sakata, Keren Cheng, Michinori Mayama, Yasunari Seita, Andrea J Detlefsen, Clementina A Mesaros, Trevor M Penning, Kyosuke Shishikura, Wenli Yang, Richard J Auchus and 2 more

Open access · greenAbstract read
In one paragraph

Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
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  4. Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025
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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

12 authors at 4 institutions in 1 country.

Yuka SakataDepartment of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Keren ChengDepartment of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michinori MayamaDepartment of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yasunari SeitaDepartment of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Bell Research Center for Reproductive Health and Cancer, Nagoya 460-0003, Japan.
Andrea J DetlefsenDepartment of Biochemistry and Biophysics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
Clementina A MesarosDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trevor M PenningDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kyosuke ShishikuraDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wenli YangInstitute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Richard J AuchusDivision of Metabolism, Endocrinology, and Diabetes, Departments of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, MI 48105, USA.
Jerome F StraussDepartment of Obstetrics and Gynecology, University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kotaro SasakiDepartment of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: ksasaki@upenn.edu.
California Institute for Regenerative Medicine · USUniversity of Pennsylvania · USTranslational Therapeutics (United States) · USUniversity of Michigan · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

The mechanisms leading to adrenal cortex development and steroid synthesis in humans remain poorly understood due to the paucity of model systems. Herein, we recapitulate human fetal adrenal cortex specification processes through stepwise induction of human-induced pluripotent stem cells through posterior intermediate mesoderm-like and adrenocortical progenitor-like states to ultimately generate fetal zone adrenal-cortex-like cells (FZLCs), as evidenced by histomorphological, ultrastructural, and transcriptome features and adrenocorticotropic hormone (ACTH)-independent Δ5 steroid biosynthesis. Furthermore, FZLC generation is promoted by SHH and inhibited by NOTCH, ACTIVIN, and WNT signaling, and steroid synthesis is amplified by ACTH/PKA signaling and blocked by inhibitors of Δ5 steroid synthesis enzymes. Finally, NR5A1 promotes FZLC survival and steroidogenesis. Together, these findings provide a framework for understanding and reconstituting human adrenocortical development in vitro, paving the way for cell-based therapies of adrenal insufficiency.

Indexed as

Adrenal CortexInduced Pluripotent Stem CellsAdrenocorticotropic HormoneHumansSteroidsWnt Signaling PathwayAdrenocorticotropic HormoneSteroidsadrenal capsuleadrenal cortexadrenocortical developmentadrenocorticotropic hormonedefinitive zonefetal zonehuman-induced pluripotent stem cellsintermediate mesodermNR5A1steroidogenesis

Identifiers

PMID36413950
PMCPMC9927873
OpenAlexW4309780443

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.