Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation^☆

Abstract

Background: Terminal erythroid differentiation (TED) is the maturation process of proerythroblasts into enucleated erythrocytes. Animal models are essential for studying red blood cell disorders.

Methods: We isolated erythroblasts at different TED stages from mouse bone marrow using FACS and performed integrated multi-omics analyses.

Results: We developed a stage-specific transcriptome and proteome profile, enhancing murine TED databases. The most significant changes occurred during the transition from proerythroblasts to basophilic erythroblasts, characterized by immune function suppression and activation of erythroid processes. Global gene and protein expression dynamics showed that orthochromatic erythroblasts exit the cell cycle, with transcription cofactors histone deacetylase 1(HDAC1), histone deacetylase 2(HDAC2), and cell division control protein 6 homolog (CDC6), playing key roles in cell cycle regulation. Additionally, autophagy was initiated at the basophilic stage, indicated by increased autophagy-related gene (ATG) mRNA levels and activation of autophagy marker proteins like microtubule associated protein 1 light chain 3 beta (LC3-I), optineurin (OPTN), and ATGs, including Atg7, Atg4b, Atg3, and Atg2b.

Conclusions: Overall, we have generated a foundational murine transcriptome and proteome dataset, providing insights into the functional dynamics and regulatory mechanisms of terminal erythroid differentiation.

Keywords

Terminal erythroid maturation / Murine / Transcriptome / Proteome

Ethics approval and consent to participate

The animal experiments were approved by the Animal Ethics Committee of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College (No. ACUC-A01-2021-032).

Authors' contributions

Xiao-Yue Tang and Jia-Huan Chen conceived the study design, performed data analysis, and drafted the manuscript. Ran Yang, Hong Fan, and Ke Yang contributed to animal experiments. Tao Ding and Qiao-Chu Wang collected the transcriptome and proteome data. Yue-Wu and Ye-Hong Yang contributed to the data analysis. Zhi-Yi Zhang and Chun-Mei Shi participated in sample collection. Xue-Hui Liu, and Jiang-Feng Liu contributed to data analysis and interpretation, and manuscript revising. Xiang Lv, and Jun-Tao Yang conceived the study design, data analysis interpretation, and manuscript revising.

Funding

This study was supported by grants from the National Key R&D Program of China (2023YFC2507102), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, China (CIFMS2022-I2M-1–011, CIFMS2021-I2M-1–044, CIFMS2022-I2M-2–001), the National Natural Science Foundation of China (82341064, 82090010, 82090011 ), the National High Level Hospital Clinical Research Funding (2025-PUMCH-C-041), and the State Key Laboratory Special Fund 2060204.

Availability of data

All the raw transcriptomic data were deposited in the GEO (GSE229589). All proteomic and phosphoproteomic raw data have been deposited in the ProteomeXchange Consortium through iProx [45] with the identifiers IPX0008786002 and IPX0008786002, respectively. All other data generated or analyzed during this study were included in the published article.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

Not applicable.

Consent for publication

Not applicable.

Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.gmg.2025.100083.

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