Evidence map›Paper›PMID 40220298›Full record

ArticleCell reports2025

HAND1, partially mediated through ape-specific LTR binding, is essential for human extra-embryonic mesenchyme derivation from iPSCs.

Zukai Liu, Yuliana Tan, William F Flynn, Lili Sun, Ponthip Pratumkaew, Juliana Alcoforado Diniz, Nelio A J Oliveira, Justin A McDonough, William C Skarnes, Paul Robson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. CHD8-Dependent Chromatin Licensing Sustains Trophoblast Stem Cell Transcriptional Programs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
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

10 authors.

Zukai LiuThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
Yuliana TanThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
William F FlynnThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Lili SunThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Ponthip PratumkaewThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Juliana Alcoforado DinizThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Nelio A J OliveiraThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Justin A McDonoughThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
William C SkarnesThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
Paul RobsonThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06030, USA. Electronic address: paul.robson@jax.org.

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Paul Robson · 1985 to 2026
$61.9M
The KAPP-Sen Tissue Mapping Center CollaborativeU54AG075941 · NIA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI KUCHEL, GEORGE A · 2021 to 2025
$13.8M
JAX MorPhiC Data Production CenterUM1HG012651 · NHGRI · JACKSON LABORATORY · PI Paul Robson, William Carl Skarnes · 2022 to 2026
$9.6M
NCI NIH HHS P30 CA034196NHGRI NIH HHS UM1 HG012651NIA NIH HHS U54 AG075941
6 · The paper itself

Abstract

The specification of extra-embryonic mesenchyme (ExMC) is a prime example of developmental divergence between mouse and human. Derived from definitive mesoderm during mouse gastrulation, the human ExMC first appears at peri-implantation prior to gastrulation and therefore its human cellular origin, still unknown, must differ. In a human pluripotent stem cell model, we report that ExMC shares progenitor cells with trophoblast, suggesting a trophectoderm origin. This ability to form ExMC appears to extend to human trophoblast stem cell lines. We define HAND1 as an essential regulator of ExMC specification, with null cells remaining in the trophoblast lineage. Bound by HAND1, ape-specific, endogenous retrovirus-derived LTR2B contributes to unique features of ExMC. Additionally, ExMC supports the maintenance of pluripotent stem cells, possibly reflecting a role in maintaining epiblast pluripotency through peri-implantation development. Our data emphasize the nascent evolutionary innovation in human early development and provide a cellular system to study this.

Indexed as

Induced Pluripotent Stem CellsMesodermTerminal Repeat SequencesAnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationCell LineEndogenous RetrovirusesHumansMiceProtein BindingTrophoblastsBasic Helix-Loop-Helix Proteinshelix-loop-helix protein, eHANDblastocystBMP4CP: Molecular biologyCP: Stem cell researchembryonic modelevolutionextra-embryonic mesodermHAND1LTR2Btransposable elementtrophoblast

Identifiers

PMID40220298
PMCPMC12082684

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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.