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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2500269


Single-cell profiling of liver in offspring with intrauterine hyperglycemia reveals acute-phase response deficiency


Author(s):  Jiahang MO1*, Jing YAN1*, Yi CHENG2*, Kaixuan DONG3, Tianyou WANG4, Jie LI1, Meijun PAN1, Guolian DING1, 5, Hong ZHU1, 5, Hefeng HUANG1, 5, 6, 7

Affiliation(s):  1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai 200090, China 2The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China 4Department of Gynecology Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200090, China 5Shanghai Key Laboratory of Reproduction and Development, Shanghai 200032, China 6Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; more

Corresponding email(s):   Hong ZHU, Zhuhong-hope@163.com Hefeng HUANG, huanghefg@hotmail.com

Key Words:  Intrauterine hyperglycemia (IHG), Single-cell RNA sequencing (sc-RNA seq), Liver, Myeloid cell, Inflammation, Acute-phase response


Jiahang MO1*, Jing YAN1*, Yi CHENG2*, Kaixuan DONG3, Tianyou WANG4, Jie LI1, Meijun PAN1, Guolian DING1,5, Hong ZHU1,5, Hefeng HUANG1,5,6,7. Single-cell profiling of liver in offspring with intrauterine hyperglycemia reveals acute-phase response deficiency[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .

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Abstract: 
Gestational diabetes mellitus (GDM) has long-term effects on offspring health. In the development of this chronic disease, inflammatory profiles play important roles. However, the assessment of GDM fetuses for their inflammatory status has been limited. Thus, single-cell RNA sequencing (scRNA-seq) is urgently needed to delineate the inflammatory characteristics of offspring with intrauterine hyperglycemia (IHG). Methods: A mouse IHG model was induced by streptozotocin (STZ). liver samples of offspring at the fetal and adult periods were collected for scRNA-seq analysis and further experiments. CytoTRACE and Monocle were used for the developmental analysis of fetal liver after dimension reduction and clustering. The CellChat algorithm was applied for the cellular interaction analysis of adult livers. A lipopolysaccharide (LPS)-induced sepsis model was built in adult offspring to evaluate the immune response. Subsequently, primary cell flow cytometry (FCM) of the bone marrow (BM) and liver was performed for myeloid lineage detection. Finally, the transcriptional and translational levels of acute-phase response cytokines were quantified. Results: Our study has mapped the single-cell profile of livers in offspring with IHG. Myeloid polarization was identified, accompanied by the developmental retardation of multiple cell lineages in IHG offspring. In adults, myeloid polarization was restored to some extent, while the proinflammatory potential of these myeloid cells seemed to be deeply molded. Adult offspring with IHG also showed deficiency in acute-phase response in the LPS-induced sepsis model. Conclusions: The single-cell profile of livers from offspring with IHG highlighted the comprehensive inflammatory status of the myeloid lineage and hinted acute-phase response deficiency in sepsis.

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