Evidence map›Paper›PMID 42443522›Full record

ArticleCell research2026

A universal 6iL/E4 culture system for deriving and maintaining embryonic stem cells across mammalian species.

Duo Wang, Hao Ming, Dongshan Yang, Xiang Cui, Zachary Freeman, Li-Kuang Tsai, Zhuying Wei, Liu Liu, Giovanna Nascimento Scatolin, Brian Bennett and 26 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Developing stem cell-based bovine embryos for in vitro breeding.The Journal of reproduction and development · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 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, USA. wangduotc@gmail.com.ORCID 0009-0001-5060-8968
Hao MingDepartment of Animal Sciences, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
Dongshan YangCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0003-2449-8651
Xiang CuiCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.
Zachary FreemanTransgenic Animal Model Core, University of Michigan Medical School, Ann Arbor, MI, USA.
Li-Kuang TsaiCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.
Zhuying WeiCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.
Liu LiuGilbert S. Omenn Department of Computational Medicine and Bioinformatics, Ann Arbor, MI, USA.
Giovanna Nascimento ScatolinDepartment of Animal Sciences, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
Brian BennettEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, USA.
Xiukun WangEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, 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, 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, USA.
Shuling WangTransgenic Mouse Facility, University of California, Irvine, CA, USA.
Kai-Xuan ShiTransgenic Mouse Facility, University of California, Irvine, CA, USA.
Denis EvseenkoDepartment of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Ben Van HandelDepartment of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Longhua GuoDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Xiaoting DaiDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Youcai XiongCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, 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, USA.
Yinjuan WangSchool of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Rajan IyyappanDepartment of Animal Sciences, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-6356-7093
Oscar Alejandro Ojeda-RojasDepartment of Large Animal Clinical Sciences, University of Florida, Gainesville, FL, USA.
Guang HuEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, 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, USA.
Xiangbo KongCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.
Xiaofeng XiaATGC Inc., Philadelphia, PA, USA.
Jifeng ZhangCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.
Y Eugene ChenCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.
Zongliang JiangDepartment of Animal Sciences, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA. z.jiang1@ufl.edu.
Jie XuCenter for Advanced Models Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA. jiex@umich.edu.
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, USA. qying@med.usc.edu.ORCID 0000-0001-5822-9498

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
Targeting SGLTs for liver disease in a rabbit model of cystic fibrosisR01DK134361 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JIE XU, Kezhong Zhang · 2023 to 2026
$2.5M
Targeted editing of ASGR1 for cardiovascular diseasesR01HL169976 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI YUQING Eugene CHEN, Renzhi Han · 2024 to 2026
$2.1M
National Center of Rabbit Models for Translational ResearchR24OD039745 · OD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Zachary Thomas Freeman · 2025 to 2026
$1.6M
Chicken embryonic stem cellsR01GM151373 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Qilong Ying · 2023 to 2026
$1.3M
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
NHLBI NIH HHS R01 HL169976NICHD NIH HHS R01 HD102533NIDDK NIH HHS R01 DK134361NIGMS NIH HHS R01 GM129305NIGMS NIH HHS R01 GM151373NIH HHS R24 OD039745NIH HHS R41 OD023245U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 1R01HD102533U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL169976U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK134361U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM129305U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM151373U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) R24OD039745U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) R41OD023245
6 · The paper itself

Abstract

The derivation of authentic embryonic stem cells (ESCs) across mammalian species remains a major challenge. Here, we report the development of a defined, serum-free culture system, termed 6iL/E4, that enables the derivation and long-term self-renewal of ESCs across diverse mammalian species. Through systematic dissection of signaling pathways, we identified conserved regulatory modules involving GSK3α, WNT, STAT3, PDGFR, and MEK/ERK signaling. The optimized 6iL/E4 conditions support stable derivation and expansion of ESCs from mouse, rat, rabbit, and bovine embryos. For rabbit, ESC derivation required supplementation with the LATS inhibitor TDI-011536 (TDI), and 6iL/TDI-cultured rabbit ESCs exhibited chimera-forming capability. In bovine ESCs, inducible expression of Klf2 and Nanog reinforced pluripotency and promoted in vivo chimeric contribution. Importantly, we demonstrated that 6iL robustly establishes and maintains human pluripotent stem cells in a naïve-like state. 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 biotechnological applications.

Indexed as

Cell Culture TechniquesEmbryonic Stem CellsAnimalsCattleCell DifferentiationCells, CulturedHumansMicePluripotent Stem CellsRabbitsRatsSignal TransductionSpecies Specificity

Identifiers

PMID42443522
PMCPMC13424318

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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.