Evidence map›Paper›PMID 40475639›Full record

ArticlebioRxiv : the preprint server for biology2025

A Universal 6iL/E4 Culture System for Deriving and Maintaining Embryonic Stem Cells Across Mammalian Species.

Duo Wang, Hao Ming, Dongshan Yang, Li-Kuang Tsai, Zhuying Wei, Giovanna Nascimento Scatolin, Xiukun Wang, Kimberly Yau, Litao Tao, Xinyi Tong and 19 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

29 authors.

Duo WangEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Hao MingDepartment of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
Dongshan YangCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Li-Kuang TsaiCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Zhuying WeiCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Giovanna Nascimento ScatolinDepartment of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
Xiukun WangEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, RTP, NC 27709, USA.
Kimberly YauDepartment of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Litao TaoDepartment of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE 68178, USA.
Xinyi TongEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Shuling WangTransgenic Mouse Facility, University of California, Irvine. Irvine, CA 92697, USA.
Kai-Xuan ShiTransgenic Mouse Facility, University of California, Irvine. Irvine, CA 92697, USA.
Denis EvseenkoDepartment of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Ben Van HandelDepartment of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Bingjing ZhangEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Yinjuan WangSchool of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA 70803, USA.
Rajan IyyappanDepartment of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
Oscar Alejandro Ojeda-RojasDepartment of Large Animal Clinical Sciences, University of Florida, Gainesville, FL 32610, USA.
Guang HuCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Lynda McGinnisDepartment of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Richard PaulsonDepartment of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Daniel MckimEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Xiangbo KongCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Xiaofeng XiaATGC Inc. 1004w 9th Avenue, Suite 10, King of Prussia, PA 19406, USA.
Jifeng ZhangCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Y Eugene ChenCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Jie XuCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
Zongliang JiangDepartment of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
Qi-Long YingEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Funding

DNA Methylation at N6-Adenine in Placental Trophoblast DevelopmentR01HD102533 · NICHD · UNIVERSITY OF FLORIDA · PI JIANG, ZONGLIANG, XIAO, ZHUO ANDREW · 2020 to 2024
$3.1M
Embryonic stem cell self-renewalR01GM129305 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YING, QILONG · 2018 to 2021
$1.3M
Ground state rabbit pluripotent stem cellsR41OD023245 · OD · ATGC, INC. · PI YING, QILONG · 2017 to 2017
$226k
NICHD NIH HHS R01 HD102533NIGMS NIH HHS R01 GM129305NIH HHS R41 OD023245
6 · The paper itself

Abstract

The derivation of authentic embryonic stem cells (ESCs) from diverse mammalian species offers valuable opportunities for advancing regenerative medicine, studying developmental biology, and enabling species conservation. Here, we report the development of a robust, serum-free culture system, termed 6iL/E4 that enables the derivation and long-term self-renewal of ESCs from multiple mammalian species, including mouse, rat, bovine, rabbit, and human. Using systematic signaling pathway analysis, we identified key regulators-including GSK3α, STAT3, PDGFR, BRAF, and LATS-critical for ESC maintenance across species. Additionally, inducible expression of KLF2 and NANOG enhances the naive pluripotency and chimeric potential of bovine ESCs. The E4 medium also supports stable ESC growth while minimizing lineage bias. These findings reveal conserved principles underlying ESC self-renewal across divergent mammalian species and provide a universal platform for cross-species stem cell research, disease modeling, and biotechnology applications.

Indexed as

6iL/E4 culturebovine ESCschimerismembryonic stem cellsGSK3αnaive pluripotencyPDGFR signalingpluripotent stem cellsrabbit ESCsspecies conservation

Identifiers

PMID40475639
PMCPMC12139945

What OpenQuestion holds

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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.