Evidence map›Paper›PMID 35394424›Full record

ArticleeLife2022

Efficient differentiation of human primordial germ cells through geometric control reveals a key role for Nodal signaling.

Kyoung Jo, Seth Teague, Bohan Chen, Hina Aftab Khan, Emily Freeburne, Hunter Li, Bolin Li, Ran Ran, Jason R Spence, Idse Heemskerk

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
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

44 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
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  6. Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026
    Review
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  20. Primate amnion development.Development (Cambridge, England) · 2024
    Review
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 at 1 institution in 1 country.

Kyoung JoDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Seth Teague *Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States.
Bohan Chen *Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.ORCID 0000-0002-9781-2982
Hina Aftab Khan *Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Emily FreeburneDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.ORCID 0000-0003-0344-577X
Hunter LiDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Bolin LiDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Ran RanDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.ORCID 0000-0001-7869-3992
Idse HeemskerkDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.ORCID 0000-0002-8861-7712
University of Michigan · US

Funding

Multifunctional morphogens: patterning precision and mesoderm migrationR35GM138346 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HEEMSKERK, IDSE JOANNES · 2020 to 2025
$4.3M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
A systems approach toward human primordial germ cell differentiationR01HD120309 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Idse Joannes Heemskerk · 2026 to 2026
$391k
NICHD NIH HHS R01 HD120309NIGMS NIH HHS R35 GM138346NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

Human primordial germ cells (hPGCs) form around the time of implantation and are the precursors of eggs and sperm. Many aspects of hPGC specification remain poorly understood because of the inaccessibility of the early postimplantation human embryo for study. Here, we show that micropatterned human pluripotent stem cells (hPSCs) treated with BMP4 give rise to hPGC-like cells (hPGCLC) and use these as a quantitatively reproducible and simple in vitro model to interrogate this important developmental event. We characterize micropatterned hPSCs up to 96 hr and show that hPGCLC populations are stable and continue to mature. By perturbing signaling during hPGCLC differentiation, we identify a previously unappreciated role for Nodal signaling and find that the relative timing and duration of BMP and Nodal signaling are critical parameters controlling the number of hPGCLCs. We formulate a mathematical model for a network of cross-repressive fates driven by Nodal and BMP signaling, which predicts the measured fate patterns after signaling perturbations. Finally, we show that hPSC colony size dictates the efficiency of hPGCLC specification, which led us to dramatically improve the efficiency of hPGCLC differentiation.

Indexed as

Germ CellsPluripotent Stem CellsCell DifferentiationEmbryonic DevelopmentHumansSignal Transductioncell fate patterningcell signalingcomputational biologydevelopmental biologyhumanhuman pluripotent stem cellsmicropatterningprimordial germ cellssystems biology

Identifiers

PMID35394424
PMCPMC9106331
OpenAlexW4226089669

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.