Evidence map›Paper›PMID 37726790›Full record

ArticleJournal of ovarian research2023

CRISPR/Cas9-mediated activation of NR5A1 steers female human embryonic stem cell-derived bipotential gonadal-like cells towards a steroidogenic cell fate.

Laura Danti, Karolina Lundin, Kirsi Sepponen, Dawit A Yohannes, Juha Kere, Timo Tuuri, Juha S Tapanainen

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of ovarian research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Laura DantiDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland.
Karolina LundinDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland.
Kirsi SepponenDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland.
Dawit A YohannesDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland.
Juha KereFolkhälsan Research Centre, Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, 00290, Finland.
Timo TuuriDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland.
Juha S TapanainenDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland. juha.tapanainen@helsinki.fi.
University of Helsinki · FIHelsinki University Hospital · FIKarolinska Institutet · SE

Funding

European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie 813707
6 · The paper itself

Abstract

The nuclear receptor subfamily 5 group A member 1 (NR5A1), encoding steroidogenic factor 1 (SF-1), has been identified as a critical factor in gonadal development in animal studies. A previous study of ours suggested that upregulation of NR5A1 during early gonadal differentiation in male (46,XY) human pluripotent stem cells steers the cells into a more mature gonadal cell type. However, the detailed role of NR5A1 in female gonadal differentiation has yet to be determined. In this study, by combining the processes of gonadal differentiation and conditional gene activation, we show that NR5A1 induction predominantly upregulates the female gonadal marker inhibin subunit α (INHA) and steroidogenic markers steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 17 subfamily A member 1 (CYP17A1), hydroxy-delta-5-steroid dehydrogenase (HSD3B2) and hydroxysteroid 17-beta dehydrogenase 1 (HSD17B1). In contrast, NR5A1 induction did not seem to affect the bipotential gonadal markers gata binding protein 4 (GATA4) and Wilms' tumour suppressor 1 (WT1) nor the female gonadal markers r-spondin 1 (RSPO1) and wnt family member 4 (WNT4). Differentially expressed genes were highly associated with adrenal and ovarian steroidogenesis pathways. Moreover, time-series analysis revealed different dynamic changes between male and female induced samples, where continuously upregulated genes in female gonadal differentiation were mostly associated with adrenal steroidogenesis. Thus, in contrast to male gonadal differentiation, NR5A1 is necessary but not sufficient to steer human embryonic stem cell (hESC)-derived bipotential gonadal-like cells towards a more mature somatic, female cell fate. Instead, it seems to direct bipotential gonadal-like cells more towards a steroidogenic-like cell population. The information obtained in this study helps in elucidating the role of NR5A1 in gonadal differentiation of a female stem cell line.

Indexed as

Human Embryonic Stem CellsAnimalsCell DifferentiationCRISPR-Cas SystemsCytochrome P450 Family 17FemaleHumansMaleSteroidogenic Factor 1Cytochrome P450 Family 17NR5A1 protein, humanSteroidogenic Factor 1CRISPRGonadal developmentNR5A1Orphan nuclear receptorOvarySF-1Stem cellsSteroidogenesisTestis

Identifiers

PMID37726790
PMCPMC10510196
OpenAlexW4386878569

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.