# Molecular architecture of mesoderm cells across early to middle stage of human embryo development at single-cell resolution

**Authors:** Wei Zhang, Haiyan Yu, Zhibin Zhang, Dandan Li, Yane Yang, Wei Shi, Wenting Li, Yan Jiang, Wenlong Hu, Zhipeng Zeng, Xinqiong Liu, Zhanye Zheng, Minglin Ou, Donge Tang, Yong Dai

PMC · DOI: 10.1186/s12860-025-00561-9 · BMC Molecular and Cell Biology · 2025-12-25

## TL;DR

This study reveals the molecular architecture of mesoderm cells during early human embryo development, offering insights into organ formation and regenerative medicine.

## Contribution

The study identifies key genes and cell sub-clusters involved in mesoderm cell differentiation into core organs at single-cell resolution.

## Key findings

- EGR1 is potentially relevant to the differentiation of mesoderm cell sub-clusters.
- RPL10P9+PTMAP5+ mesoderm cells show expression profiles similar to endocardial cells.
- NDUFA4L2+A2M+ mesoderm cells can form endothelial and hematopoietic stem cells, with MEF2C involvement.

## Abstract

The differentiation of mesodermal cells (MCs) in the early stage of embryonic development contributes to the organogenesis of several core organs. However, the single-cell molecular architecture of MCs and the key molecular events during the differentiation remain unclear.

We performed single-cell RNA sequencing (RNA sequencing) and single-cell assay for transposase-accessible chromatin (ATAC-Seq) to analyze the developmental features of MCs to heart, kidney, spleen, liver, and brain in human embryos at gestational ages 7–17 weeks.

We found that EGR1 might be relevant to the differentiation of heterogeneous MC sub-clusters. Meanwhile, RPL10P9+PTMAP5+ MCs had the closest expression profiling with endocardial cells. NDUFA4L2+A2M+ MCs presented the potentials to form endothelial cells (ECs) and hematopoietic stem cells, and MEF2C might be involved in this process.

These findings provide insights into the molecular architecture and lineage progression of MCs during early human embryonic organogenesis, offering a valuable reference for regenerative medicine and organ bioengineering.

The online version contains supplementary material available at 10.1186/s12860-025-00561-9.

## Linked entities

- **Genes:** EGR1 (early growth response 1) [NCBI Gene 1958], RPL10P9 (ribosomal protein L10 pseudogene 9) [NCBI Gene 389342], PTMAP5 (prothymosin alpha pseudogene 5) [NCBI Gene 150928], COXFA4L2 (cytochrome c oxidase hypoxia associated subunit FA4L2) [NCBI Gene 56901], A2M (alpha-2-macroglobulin) [NCBI Gene 2], MEF2C (myocyte enhancer factor 2C) [NCBI Gene 4208]

## Full-text entities

- **Genes:** COXFA4L2 (cytochrome c oxidase hypoxia associated subunit FA4L2) [NCBI Gene 56901] {aka MISTRH, NDUFA4L2, NUOMS}, RPL10P9 (ribosomal protein L10 pseudogene 9) [NCBI Gene 389342] {aka RPL10_1_637}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, PTMAP5 (prothymosin alpha pseudogene 5) [NCBI Gene 150928], MEF2C (myocyte enhancer factor 2C) [NCBI Gene 4208] {aka C5DELq14.3, DEL5q14.3, NEDHSIL}
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12849250