Evidence map›Paper›PMID 41509310›Full record

ArticlebioRxiv : the preprint server for biology2026

Fezf2 regulates differentiation of Aire-expressing and post-Aire mimetic epithelial populations maintaining thymic homeostasis.

Joe Germino, Xian Liu, Yi Wang, Jared Balolong, Vera Tang, Im-Hong Sun, Yanzhen Nie, Jeremiah Tsyporin, Irina Proekt, Kristin Rattay and 5 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Joe GerminoDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Xian LiuDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Yi WangDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jared BalolongDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Vera TangDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Im-Hong SunDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Yanzhen NieDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
Jeremiah TsyporinDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
Irina ProektDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Kristin RattayPharmacological Institute, Biochemical Pharmacological Center, University of Marburg, Marburg, Germany.
Vasilis NtranosDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Mark S AndersonDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Bin ChenDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
James M GardnerDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Corey N MillerDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Funding

Lineage Progression of Cortical Neural Stem CellsR01NS089777 · NINDS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI CHEN, BIN · 2015 to 2025
$4.7M
Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Thymic medullary epithelial cell turnover and control of immune toleranceR37AI097457 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mark S Anderson · 2017 to 2026
$4.0M
Transcriptional regulation of neuronal identity and connectivityR01MH094589 · NIMH · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI CHEN, BIN · 2011 to 2021
$3.7M
Mechanisms of thymic stromal-immune crosstalk for homeostasis and naïve T cell licensing across lifeK01AG072789 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, COREY NICHOLAS · 2021 to 2025
$701k
NIAID NIH HHS R37 AI097457NIA NIH HHS K01 AG072789NIGMS NIH HHS T32 GM136547NIMH NIH HHS R01 MH094589NINDS NIH HHS R01 NS089777
6 · The paper itself

Abstract

Fezf2 has been proposed to serve principally as a transcriptional regulator of broad self-antigen expression in medullary thymic epithelial cells (mTECs). Here, we demonstrate an additional function for Fezf2 as a developmental regulator of TEC lineage commitment. Fezf2 deficiency in the thymus led to a relative expansion of lung mimetic and Ccl21+ immature mTECs at the expense of MHCII-hi Aire-expressing and all other mimetic populations. Consistent with this, the disruption of mTEC development had functional consequences, including alterations in tuft-associated iNKT polarization and microfold-associated B-cell class switching. In addition, high-resolution transcriptomics revealed that Fezf2 and Aire regulate distinct transcriptional programs, with Fezf2 driving both activation and repression of a more limited set of tissue-restricted genes compared to the broad gene activation program observed for Aire. Pure transcriptional repression at Fezf2 target loci was sufficient to partially rescue mTEC development in global Fezf2-/- (tKO) mice, potentially through suppression of Lifr expression and modulation of downstream Stat3 signaling tone. These results expand our understanding of Fezf2 in mTEC biology, highlighting transcriptional repression as a required functional facet for adult steady-state lineage patterning across the mTEC compartment.

Identifiers

PMID41509310
PMCPMC12776557

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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.