Human primordial germ cell heterogeneity in vitro is associated with distinctive biological states.

Young Sun Hwang, Qiu Ya Wu, Sissy E Wamaitha, Amander T Clark

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Article in Cellular & molecular biology letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 authors.

Young Sun HwangDepartment of Molecular, Cell, and Developmental Biology, Eli and Edyth Broad Center for Regenerative Medicine and Stem Cell Research, Center for Reproductive Science, Health and Education, University of California, Los Angeles (UCLA), Los Angeles, 90095, CA, USA.

Qiu Ya WuDepartment of Molecular, Cell, and Developmental Biology, Eli and Edyth Broad Center for Regenerative Medicine and Stem Cell Research, Center for Reproductive Science, Health and Education, University of California, Los Angeles (UCLA), Los Angeles, 90095, CA, USA.

Sissy E WamaithaDepartment of Molecular, Cell, and Developmental Biology, Eli and Edyth Broad Center for Regenerative Medicine and Stem Cell Research, Center for Reproductive Science, Health and Education, University of California, Los Angeles (UCLA), Los Angeles, 90095, CA, USA.

Amander T ClarkDepartment of Molecular, Cell, and Developmental Biology, Eli and Edyth Broad Center for Regenerative Medicine and Stem Cell Research, Center for Reproductive Science, Health and Education, University of California, Los Angeles (UCLA), Los Angeles, 90095, CA, USA. clarka@ucla.edu.ORCID https://orcid.org/0000-0003-2483-3982

Funding

Differentiating embryonic stem cells into developing germ lineR01HD079546 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLARK, AMANDER · 2015 to 2024

$3.7M

NICHD NIH HHS R01 HD079546NIH HHS R01HD079546

6 · The paper itself

Abstract

backgroundPrimordial germ cells (PGCs) exhibit molecular heterogeneity during development, yet whether this reflects functionally distinct states remains unclear.

methodsWe investigated the functional significance of DND1 translation heterogeneity in human PGC-like cell (hPGCLC) extended culture, using dual fluorescent reporters, transcriptomic analysis and functional assays.

resultsSingle-cell RNA-sequencing revealed that DND1 + hPGCLCs are enriched in RNA regulatory genes including those associated with P-bodies and translational control. DND1 + cells exhibit reduced proliferation, cell cycle exit, and elevated nuclear expression P27 (CDKN1B). These cells also maintained stable expression of genes essential for germ cell differentiation. Notably, BMP2 supplementation stabilized DND1 translation without altering mRNA levels or proliferation rates.

conclusionsTogether, these findings demonstrate that post-transcriptional regulation by DND1 coordinates cell cycle dynamics with distinct cellular state in human germ cells, highlighting critical translational control mechanisms in germline development.

Indexed as

Germ CellsCell CycleCell DifferentiationCell ProliferationCyclin-Dependent Kinase Inhibitor p27DEAD-box RNA HelicasesHumansProtein BiosynthesisCyclin-Dependent Kinase Inhibitor p27DDX4 protein, humanDEAD-box RNA HelicasesCell cycle exitDead end 1Extended cultureHeterogeneityHuman in vitro germ cellsPost-transcriptional regulation

Identifiers

PMID42343208

DOI10.1186/s11658-026-00986-w

PMCPMC13560305

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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.