Evidence map›Paper›PMID 36803359›Full record

ArticleeLife2023

Directed differentiation of human iPSCs to functional ovarian granulosa-like cells via transcription factor overexpression.

Merrick D Pierson Smela, Christian C Kramme, Patrick R J Fortuna, Jessica L Adams, Rui Su, Edward Dong, Mutsumi Kobayashi, Garyk Brixi, Venkata Srikar Kavirayuni, Emma Tysinger and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in eLife, 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 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
20.9field-weighted citation impact, top 1% 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

59 citing papers in PubMed, 68 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Merrick D Pierson Smela *Wyss Institute, Harvard University, Boston, United States.ORCID https://orcid.org/0000-0001-5816-7098
Christian C Kramme *Wyss Institute, Harvard University, Boston, United States.ORCID https://orcid.org/0000-0002-7518-8111
Patrick R J FortunaWyss Institute, Harvard University, Boston, United States.
Jessica L AdamsWyss Institute, Harvard University, Boston, United States.
Rui SuWyss Institute, Harvard University, Boston, United States.
Edward DongWyss Institute, Harvard University, Boston, United States.
Mutsumi KobayashiMassachusetts General Hospital Center for Cancer Research, Harvard Medical School, Charlestown, United States.ORCID https://orcid.org/0000-0001-7897-2633
Garyk BrixiWyss Institute, Harvard University, Boston, United States.
Venkata Srikar KavirayuniDepartment of Biomedical Engineering, Duke University, Durham, United States.
Emma TysingerDepartment of Biomedical Engineering, Duke University, Durham, United States.ORCID https://orcid.org/0000-0002-3958-8097
Richie E KohmanWyss Institute, Harvard University, Boston, United States.ORCID https://orcid.org/0000-0002-7412-671X
Toshi ShiodaMassachusetts General Hospital Center for Cancer Research, Harvard Medical School, Charlestown, United States.ORCID https://orcid.org/0000-0002-9434-7835
Pranam ChatterjeeWyss Institute, Harvard University, Boston, United States.ORCID https://orcid.org/0000-0003-3957-8478
George M ChurchWyss Institute, Harvard University, Boston, United States.ORCID https://orcid.org/0000-0003-3535-2076
Harvard University · USDuke University · US

Funding

Applications of the long-term culture human primordial germ cell-like cells to toxicological assessments and mechanistic studies on chemically caused heritable human health threatsR21ES034468 · NIEHS · MASSACHUSETTS GENERAL HOSPITAL · PI SHIODA, TOSHIHIRO · 2023 to 2024
$459k
Roles of the LTR5_Hs human-specific endogenous retroviruses in primordial germ cellsR21HD110839 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI SHIODA, TOSHIHIRO · 2023 to 2024
$459k
Human iPSC-derived ovarian follicles as a model of female reproductionF31HD108898 · NICHD · HARVARD UNIVERSITY · PI PIERSON SMELA, MERRICK DE FOREST · 2022 to 2024
$98k
NICHD NIH HHS F31 HD108898NICHD NIH HHS R21 HD110839NIEHS NIH HHS R21 ES034468
6 · The paper itself

Abstract

An in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and several types of somatic cells. Among these, granulosa cells play a key role in follicle formation and support for oogenesis. Whereas efficient protocols exist for generating human primordial germ cell-like cells (hPGCLCs) from human induced pluripotent stem cells (hiPSCs), a method of generating granulosa cells has been elusive. Here, we report that simultaneous overexpression of two transcription factors (TFs) can direct the differentiation of hiPSCs to granulosa-like cells. We elucidate the regulatory effects of several granulosa-related TFs and establish that overexpression of NR5A1 and either RUNX1 or RUNX2 is sufficient to generate granulosa-like cells. Our granulosa-like cells have transcriptomes similar to human fetal ovarian cells and recapitulate key ovarian phenotypes including follicle formation and steroidogenesis. When aggregated with hPGCLCs, our cells form ovary-like organoids (ovaroids) and support hPGCLC development from the premigratory to the gonadal stage as measured by induction of DAZL expression. This model system will provide unique opportunities for studying human ovarian biology and may enable the development of therapies for female reproductive health.

Indexed as

Induced Pluripotent Stem CellsTranscription FactorsCell DifferentiationFemaleHumansOogenesisOvaryTranscription Factorsdevelopmental biologygranulosahumanmouseoogenesisovaryregenerative medicinestem cellstranscription factors

Identifiers

PMID36803359
PMCPMC9943069
OpenAlexW4321366558

What OpenQuestion 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 OpenQuestion graph.