This file was generated on 2025-04-01 by Hao Huang
This document is licensed under the Creative Commons CC-BY-4.0 International License

A GENERAL INFORMATION

1. Title of the dataset: Image data used for quantification in publication "Developmental programming of Kupffer cells by maternal obesity causes fatty liver disease in the offspring"

2. Brief description of the research project and its aims:
Kupffer cells (KCs) are tissue-resident macrophages which colonize the liver early during embryogenesis. Upon liver colonization, KCs rapidly acquire a tissue-specific transcriptional signature, mature alongside the developing liver, and adapt to its functions. Throughout development and adulthood, KCs perform distinct core functions essential for liver and organismal homeostasis, including supporting fetal erythropoiesis, postnatal erythrocyte recycling, and liver metabolism. However, whether perturbations of macrophage core functions during development contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a mouse model of maternal obesity to perturb KC functions during gestation. We show that offspring exposed to maternal obesity develop fatty liver disease, driven by aberrant developmental programming of KCs that persists into adulthood. Programmed KCs promote lipid uptake by hepatocytes through apolipoprotein secretion. KC depletion in neonates born to obese mothers, followed by replenishment with naïve monocytes, rescues fatty liver disease. Further, genetic ablation of hypoxia-inducible factor alpha (Hif1a) in macrophages during gestation prevents the metabolic programming of KCs from oxidative phosphorylation to glycolysis, thereby averting the development of fatty liver disease. These results establish developmental perturbation of KC functions as a causal factor in fatty liver disease in adulthood and position fetal-derived macrophages as critical intergenerational messengers within the concept of developmental origins of health and diseases. 

3. Author Information
	A. Investigator Contact Information
		Name: Dr. Hao Huang
		Institution: Life & Medical Sciences (LIMES) Institute, University of Bonn
		Address: Carl-Troll-Str. 31, 53113 Bonn
		Email: hao.huang@uni-bonn.de
                 ORCID: 0000-0003-3878-3947

	B. Project Supervisor (Principal Investigator) Contact Information
		Name: Prof. Dr. Elvira Mass
		Institution: Life & Medical Sciences (LIMES) Institute, University of Bonn
		Address: Carl-Troll-Str. 31, 53113 Bonn
		Email: elvira.mass@uni-bonn.de
                 ORCID: 0000-0003-2318-2356

	C. In case of questions related to this dataset, please contact:
	         Name: Prof. Dr. Elvira Mass
		Institution: Life & Medical Sciences (LIMES) Institute, University of Bonn
		Address: Carl-Troll-Str. 31, 53113 Bonn
		Email: elvira.mass@uni-bonn.de

4. Date of data collection range from 2018-03-04 to 2025-03-26 

5. Information about funding sources that supported the collection of the data:
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy-EXC2151-390873048, SFB1454 

6. Language of the dataset: English

7. Geographic location of data collection:  Bonn, Germany

B DATA & FILE OVERVIEW

File List: 

“Maternal Obesity Oil-red-O WT cohort.zip” contains all Oil-red-O (ORO) staining pictures taken with a 40X object. Mice were of C57BL/6 Jrcc WT background.There are in total 6 diet groups indicated with CD meaning control diet, HFD standing for high fat diet. The first diet is the diet of the bearing dam, the second is the diet of the foster mother, and the third is the diet the mice received after weaning. All pictures were used to quantify the lipid content of the liver, shown as “ORO Area (%)” in the figure of the linked publication.

“Maternal Obesity Oil-red-O Hif1a cohort.zip” contains all Oil-red-O (ORO) staining pictures taken with a 40X object. There are in total 4 diet groups indicated with CD meaning control diet, HFD standing for high fat diet. The first diet is the diet of the bearing dam and foster mother, and the second is the diet the mice received after weaning. There are 2 genotypes, WT is Hif1a-f/f; LysM-Cre/+ and KO is Hif1a-f/f; LysM-+/+ litter mate. All pictures were used to quantify the lipid content of the liver, shown as “ORO Area (%)” in the figure of the linked publication.

“Maternal Obesity Oil-red-O Clec4f-DTR cohort.zip” contains all Oil-red-O (ORO) staining pictures taken with a 40X object. All mice were born to HFD-fed dam, fostered by CD-fed mother, and received CD after weaning. There are 2 genotypes, Clec4f-+/+ and Clec4f-DTR/+. All mice received diphtheria toxin at postnatal day (P) 0, which induces apoptosis of Kupffer cells, and Clec4f-+/+ mice and a group Clec4f-DTR/+ mice recieved monocyte/hematopoietic stem and progenitor cell transfer at P1 (indicated as DT + cells). The group of Clec4f-DTR/+ mice receiving DT only is marked with “DT only”. All pictures were used to quantify the lipid content of the liver, shown as “ORO Area (%)” in the figure of the linked publication.

“Hif1a staining postnatal day (P) 0 liver macrophages born to high fat diet (HFD)-fed or control diet (CD)-fed dams.zip” contains immunofluorescence staining pictures of P0 liver macrophages (stained by F4/80) and the Hif1a staining signal within the liver macrophages. Individual pictures are individual cells used to quantify the ratio of Hif1a signal between nuclei and cytoplasm. Cells are either from P0 mice born to HFD-fed or CD-fed dams as indicated on the files.

“Incucyte pictures of hepatocyte lipid accumulation (LD540 signal) cultured with TNFa, ApoE or ApoA1 addition .zip” contain images of hepatocytes and their LD540 signal 2 hours after the addition of TNFa, ApoE or ApoA1. Bright field imaged were used to quantify the amount of hepatocytes. LD540 images were used to quantify the LD540 intensity, i.e. lipid content in hepatocytes. Excel file in the compressed file shows the layout of the 24-well cell culture plate for the experiment.

“Incucyte pictures of hepatocyte lipid droplet formation (LD540 signal accumulation) cultured with Kupffer cells.zip” contain images of hepatocytes and their LD540 signal at base-line (0h) or 3 or 4 hours after the addition of Kupffer cells isolated from CDCDCD or HFDCDCD mice. Bright field imaged were used to quantify the amount of hepatocytes. LD540 images were used to quantify the LD540 intensity, i.e. lipid content in hepatocytes. Excel file in the compressed file shows the layout of the 24-well cell culture plate for the experiment.

C SHARING/ACCESS INFORMATION

Links to publications that cite or use the data: https://doi.org/10.21203/rs.3.rs-3242837/v1 

Methods used for collecting the data are included in the publication.

Other datasets linked to the publication related to this dataset:
All the trancriptomics and multi-omics data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237408.
Metabolome data is available at Metabolomics Workbench where it has been assigned with the Study ID ST002754 within the same project as the Lipidome data (DOI: http://dx.doi.org/10.21228/M81D9R).
Detailed information about every package used, including all dependencies, along with their respective versions, can be found in the renv.lock file located in the GitHub repository (https://github.com/LeaSeep/MaternalObesity) generated with the renv package
A snapshot of the GitHub repository can be found on Zenodo (https://doi.org/10.5281/zenodo.14287647).