Evidence map›Paper›PMID 40661576›Full record

ArticlebioRxiv : the preprint server for biology2025

WNT signaling in human pluripotent stem cells promotes HDAC2-dependent epigenetic programs and development of retinoic acid-responsive mesoderm.

Bao Q Thai, Stephanie A Luff, Jared M Churko, Jonathan N Young, Christopher M Sturgeon, Deepta Bhattacharya

Abstract readPreprint
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

6 authors.

Bao Q ThaiDepartment of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Stephanie A LuffDepartment of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jared M ChurkoDepartment of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Jonathan N YoungDepartment of Otolaryngology, University of Arizona, Tucson, AZ.
Christopher M SturgeonDepartment of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Deepta BhattacharyaDepartment of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.ORCID 0000-0001-8377-7699

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
Infection and Inflammation as Drivers of Aging (IIDA) Predoctoral Training ProgramT32AG058503 · NIA · UNIVERSITY OF ARIZONA · PI Kristian Paul Doyle, JANKO Z. NIKOLICH · 2019 to 2026
$1.9M
Engineering pluripotent stem cells to evade and promote immunityR01EB035491 · NIBIB · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Deepta Bhattacharya, Christopher Michael Sturgeon · 2024 to 2026
$1.8M
Characterization of multilineage definitive hematopoietic progenitors from human pluripotent stem cellsR01HL172940 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI STURGEON, CHRISTOPHER MICHAEL · 2024 to 2025
$1.2M
Gates Foundation INV-002414NCI NIH HHS P30 CA023074NHLBI NIH HHS R01 HL172940NIA NIH HHS T32 AG058503NIBIB NIH HHS R01 EB035491
6 · The paper itself

Abstract

Human pluripotent stem cells (hPSCs) can be used as a scalable source of lymphocytes for adoptive cell therapies, contingent on the robust generation of definitive hematopoietic intermediates. Early WNT activation with CHIR99021 during mesoderm induction promoted the formation of KDR+ ALDH1A2+ mesodermal progenitors and subsequent generation of T cells in a retinoic acid (RA)-dependent manner. Integrated scRNA-seq and ATAC-seq defined a WNT-dependent developmental trajectory from hPSCs to KDR+ ALDH1A2+ mesoderm. Gene regulatory network modeling predicted HDAC2 and E-box transcription factors as regulators of RA-responsive mesodermal differentiation downstream of WNT. HDAC2 knockout impaired, while HDAC2 overexpression enhanced, KDR+ ALDH1A2+ progenitor formation. E-box factor manipulation had no discernible effect. An orthogonal chemical screen confirmed that HDAC2 inhibition suppressed KDR+ ALDH1A2+ mesodermal progenitors, whereas modulating histone methylation enhanced their formation. These findings reveal mechanisms by which WNT signaling promotes RA-responsive mesoderm and suggest methods to improve the generation of lymphocytes from hPSCs.

Identifiers

PMID40661576
PMCPMC12258972

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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.