Human subcutaneous and visceral adipocyte atlases uncover classical and nonclassical adipocytes and depot-specific patterns
Cite
Lazarescu, O., Ziv-Agam, M., Haim, Y., Hekselman, I., Jubran, J., Shneyour, A., Muallem, H., Zemer, A., Rosengarten-Levin, M., Kitsberg, D. and Levin, L., 2025. Human subcutaneous and visceral adipocyte atlases uncover classical and nonclassical adipocytes and depot-specific patterns. Nature Genetics, pp.1-14. https://doi.org/10.1038/s41588-024-02048-3
Abstract
Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity–difference gap. For this, we performed snRNA-seq of human subcutaneous or visceral adipose tissues (five or ten samples, respectively). Of 27,665 adipocyte nuclei in both depots, most were ‘classical’, namely enriched in lipid metabolism pathways. However, we also observed ‘nonclassical’ adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization or angiogenesis or ribosomal and mitochondrial processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via nonclassical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Last, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation and intercellular communication patterns to human fat depot differences.
Datasets
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89382240-1f92-498c-bf0d-37d94f2fda81207 cells
c43256a2-8837-41dd-b32a-2d00fd95f075104 cells
10,000-16,500 nuclei14,396 cells
Unassigned12,205 cells
unknown14,396 cells
Illumina NovaSeq 6000 (EFO:0008637)8,872 cells
Illumina NextSeq 500 (EFO:0009173)3,333 cells
iESA124,062 cells
iESA51,296 cells
iESA3514 cells
iESA4279 cells
iESA2233 cells
iESA6139 cells
iESA778 cells
Unassigned24,071 cells
diabetes mellitus2,530 cells
Cluster 03,982 cells
Cluster 13,861 cells
Cluster 23,701 cells
Cluster 33,596 cells
Cluster 43,026 cells
Cluster 52,766 cells
Cluster 61,293 cells
Cluster 71,003 cells
Cluster 8767 cells
Cluster 9514 cells
Cluster 10462 cells
Cluster 11373 cells
Cluster 12293 cells
Cluster 13279 cells
Cluster 14235 cells
Cluster 15233 cells
Cluster 16139 cells
Cluster 1778 cells
emont14,396 cells
house12,205 cells
Unassigned12,205 cells
periumbilical9,515 cells
omentum2,435 cells
mid-right abdomen1,502 cells
port site647 cells
pannus297 cells
Unassigned12,205 cells
S5,264 cells
G14,616 cells
G2M4,516 cells
SA110,484 cells
hAd17,073 cells
hAd33,875 cells
hAd42,017 cells
hAd2955 cells
SA5814 cells
SA3389 cells
hAd5227 cells
SA4220 cells
hAd7217 cells
SA2156 cells
SA687 cells
SA755 cells
hAd632 cells
10x 3' v3, single-nucleus26,601 cells
normal26,601 cells
female19,387 cells
male7,214 cells
subcutaneous abdominal adipose tissue14,396 cells
subcutaneous adipose tissue12,205 cells
European8,003 cells
Jewish Israeli6,342 cells
Arab5,863 cells
Hispanic or Latin American4,560 cells
African American1,833 cells
30-399,201 cells
40-498,540 cells
20-293,509 cells
50-592,597 cells
70-791,385 cells
60-691,369 cells
7. snRNA-seq of human visceral adipose tissue - adipocytes integrated with emont et al
ExploreReference genome
Alignment software
Subject ID
Age
Donor living at sample collection
Smoking status
Sample ID
Sample preservation method
Sample collection method
Study source
Donor BMI at collection
Sample collection year
Suspension derivation process
Suspension dissociation reagent
Library ID
Cell number loaded
Sample source
Library ID - repository
Cell type
Reported disease
Seurat clusters
Data source
Tissue source
Cell cycle
Cell subtype
Assay
Disease
Sex
Tissue
Ethnicity
Age group
GRCh38, v9815,460 cells
GRCh38, v9011,475 cells
Cell Ranger count v6.0.115,460 cells
Drop-Seq tools v2.3.0,STAR v2.7.311,475 cells
Hs2542,806 cells
34312,580 cells
42632,240 cells
33871,732 cells
Hs2551,619 cells
33821,597 cells
Hs0011,571 cells
33991,552 cells
34271,512 cells
33841,451 cells
Hs0131,321 cells
Hs0121,215 cells
33131,197 cells
33571,069 cells
Hs256939 cells
Hs266786 cells
Hs010769 cells
3350530 cells
Hs009377 cells
Hs25372 cells
41 years4,122 cells
48.6 years2,580 cells
53.4 years2,240 cells
34.3 years1,732 cells
73 years1,619 cells
41.8 years1,597 cells
29 years1,571 cells
33.5 years1,552 cells
24.5 years1,512 cells
33.7 years1,451 cells
24 years1,321 cells
36 years1,215 cells
Unassigned1,197 cells
29.3 years1,069 cells
68 years786 cells
35 years769 cells
28.6 years530 cells
53 years72 cells
True26,935 cells
Unassigned23,286 cells
current3,649 cells
f011bc53-ea15-4788-be27-caa084c5a4302,806 cells
4b230ffb-6618-4efa-b174-b97b68f8f04f2,580 cells
6c50274d-bb00-46a1-9908-56ad3cea80e22,240 cells
2888c366-2fce-4100-82dd-d09f6939d36d1,732 cells
f581e2bf-d201-4bb8-bfbf-7b72c669d4b01,619 cells
b5180dfd-a19f-4b16-bd9e-a480202ab0111,597 cells
efe16d3f-9c4a-4b02-bf76-9880f11245e41,571 cells
767a0d10-3857-4cf3-8503-7e7bcf8433271,552 cells
7f6076cf-9cd3-43ce-81fc-17e13f27bd851,512 cells
7c60d225-f306-4fa2-a322-095c5697893f1,451 cells
408edc42-9253-4e08-98d0-88d15420ff9b1,321 cells
77b46259-ad3c-40c6-97c1-b1219b257ff21,215 cells
7743aab2-d4b0-4bd1-8d44-48559ff90f871,197 cells
fbba1735-4c50-4cda-83e3-6e89cbf754631,069 cells
648cb8fa-c1d6-466c-b559-4c5a1f61f159939 cells
1e38fb29-b2dd-41f7-9598-7f75b7ccc384786 cells
997c0d4a-a76a-4bbd-be78-33a1a70a85fb769 cells
80578aa0-0580-44fe-a6ec-e27b4d470c3f530 cells
ccafcc24-f50f-4b94-93f2-8472169a35c7377 cells
f6585b80-c27b-481e-a719-943e4600a1ed72 cells
frozen in liquid nitrogen26,935 cells
surgical resection26,935 cells
Unassigned15,460 cells
Beth Israel Deaconess Medical Center6,222 cells
University of Pittsburgh Medical Center5,253 cells
23.962,806 cells
35.72,580 cells
23.82,240 cells
40.91,732 cells
24.271,619 cells
41.01,597 cells
49.31,571 cells
36.21,552 cells
44.11,512 cells
34.51,451 cells
43.21,321 cells
48.71,215 cells
Unassigned1,197 cells
39.21,069 cells
34.53939 cells
22.15786 cells
43.1769 cells
28.5530 cells
45.7377 cells
30.0472 cells
Unassigned19,004 cells
20204,647 cells
20213,284 cells
mechanical dissociation,detergent solubilization26,935 cells
0.1% Tween-2015,460 cells
Unassigned11,475 cells
96abfd20-9b37-4a38-ab08-6b563466f1442,806 cells
12c60bd7-8d70-4e45-9f42-7e9623da6d762,580 cells
9f60a7c7-6725-4fd7-bc30-6fd7cf5fd1af2,240 cells
4389c730-6758-4ee0-8d92-1a1bb8a0d0371,732 cells
a9171c6a-e6e1-448b-9490-83da8b7586711,619 cells
9ed6a522-8d27-4828-948f-4a68d83580611,597 cells
df1ff128-a34e-4fc4-9398-07bfeb794e211,552 cells
2c3cf8c1-1cff-4d9d-8f3c-f1a5b35e591f1,512 cells
3f994cc8-560c-4311-8cd7-6893e540de171,451 cells
854a3225-84a1-4563-b5af-d89862cf2c781,321 cells
005b747d-5e5a-482f-a9db-9ec180000a891,215 cells
f3ed10e6-5f33-4256-8819-33cb9ce0b8911,197 cells
5a57c094-718c-42d0-84a4-c95e05bb38981,069 cells
90fc2f47-462b-49df-91db-cc574be6e4ba939 cells
9dc55ed0-8c70-4b28-9fb6-cafda5ff0357888 cells
48223038-e656-492d-9c84-5b7519319bc4786 cells
872e9105-8576-4b9b-9220-00ddc04049ec769 cells
4a8bc228-f8eb-41c5-acbf-b6070225b164683 cells
4312a72b-2f4d-4300-9202-d79884576a8e530 cells
92ef239b-3036-4f3d-9c2b-9f3e10ef4a95377 cells
9f1b8194-14f4-4357-914a-4b3fa53c4c4b72 cells
Unassigned15,460 cells
10,000-16,500 nuclei11,475 cells
Ben-Gurion University of the Negev15,460 cells
General Community11,475 cells
Unassigned11,475 cells
SRX266569522,580 cells
SRX266569462,240 cells
SRX266569571,732 cells
SRX266569541,597 cells
SRX266569471,552 cells
SRX266569531,512 cells
SRX266569561,451 cells
SRX266569551,197 cells
SRX266569581,069 cells
SRX26656948530 cells
iEVA120,426 cells
iEVA55,327 cells
iEVA3559 cells
iEVA2346 cells
iEVA4277 cells
Unassigned22,803 cells
diabetes mellitus4,132 cells
Cluster 06,448 cells
Cluster 14,686 cells
Cluster 24,505 cells
Cluster 32,244 cells
Cluster 42,175 cells
Cluster 52,011 cells
Cluster 61,771 cells
Cluster 7608 cells
Cluster 8559 cells
Cluster 9397 cells
Cluster 10280 cells
Cluster 11277 cells
Cluster 12257 cells
Cluster 13233 cells
Cluster 14224 cells
Cluster 15171 cells
Cluster 1689 cells
house15,460 cells
emont11,475 cells
Unassigned15,460 cells
omentum10,536 cells
periumbilical939 cells
Unassigned15,460 cells
S4,432 cells
G13,656 cells
G2M3,387 cells
VA111,599 cells
hAd27,973 cells
VA52,433 cells
hAd31,647 cells
hAd6830 cells
hAd1594 cells
VA3459 cells
hAd5310 cells
VA2270 cells
VA8264 cells
VA6200 cells
VA4194 cells
hAd484 cells
VA741 cells
hAd737 cells
10x 3' v3, single-nucleus26,935 cells
normal26,935 cells
female20,650 cells
male6,285 cells
visceral fat15,460 cells
visceral abdominal adipose tissue11,475 cells
Jewish Israeli8,209 cells
European7,353 cells
Arab3,814 cells
Hispanic or Latin American2,806 cells
German2,240 cells
African American1,316 cells
Unassigned1,197 cells
40-498,299 cells
30-396,719 cells
20-296,003 cells
50-592,312 cells
70-791,619 cells
Unassigned1,197 cells
60-69786 cells
8. Differentiation path from ASPCs to adipocytes in subcutaneous adipose tissue
ExploreSubject ID
Sample ID
Sample preservation method
Sample collection method
Suspension derivation process
Suspension dissociation reagent
Cell subtype
Reported diseases
Cell type
Assay
Disease
Sex
Tissue
Ethnicity
Age
S33875,423 cells
S33824,520 cells
S33994,313 cells
S34274,203 cells
S33843,768 cells
67adc4ed-10af-4d25-9530-9a47028bffc85,423 cells
e2a7f710-b486-44e8-8d2e-39f858c862904,520 cells
b5edb514-271a-434a-ba7f-10b32743eb914,313 cells
a13dd2f8-e801-4c2b-9392-f8ffa464e7984,203 cells
08d41e84-60b7-4bc6-90e1-bfabd58b0be13,768 cells
flash-freezing22,227 cells
resection22,227 cells
mechanical dissociation,detergent solubilization22,227 cells
0.1% Tween-2022,227 cells
SA110,484 cells
ASPC 25,537 cells
ASPC 13,252 cells
ASPC 3915 cells
SA5814 cells
SA3389 cells
SA4220 cells
ASPC 5161 cells
ASPC 4157 cells
SA2156 cells
SA687 cells
SA755 cells
Unassigned17,914 cells
diabetes mellitus4,313 cells
Adipocytes12,205 cells
ASPC10,022 cells
10x 3' v3, single-nucleus22,227 cells
normal22,227 cells
female14,256 cells
male7,971 cells
subcutaneous adipose tissue22,227 cells
Jewish Israeli12,491 cells
Arab9,736 cells
33 years8,081 cells
34 years5,423 cells
41 years4,520 cells
24 years4,203 cells
9. Differentiation path from ASPCs to adipocytes in visceral adipose tissue
ExploreSubject ID
Smoking status
Sample ID
Sample preservation method
Sample collection method
Donor BMI at collection
Sample collection year
Suspension derivation process
Suspension dissociation reagent
Sample source
Cell subtype
Reported disease
Cell type
Assay
Disease
Sex
Tissue
Ethnicity
Age
Age group
S34314,813 cells
S33844,482 cells
S42633,915 cells
S33873,755 cells
S33993,070 cells
S34272,979 cells
S33822,737 cells
S33571,957 cells
S33131,934 cells
S33501,327 cells
Unassigned24,199 cells
current6,770 cells
4b230ffb-6618-4efa-b174-b97b68f8f04f4,813 cells
7c60d225-f306-4fa2-a322-095c5697893f4,482 cells
6c50274d-bb00-46a1-9908-56ad3cea80e23,915 cells
2888c366-2fce-4100-82dd-d09f6939d36d3,755 cells
767a0d10-3857-4cf3-8503-7e7bcf8433273,070 cells
7f6076cf-9cd3-43ce-81fc-17e13f27bd852,979 cells
b5180dfd-a19f-4b16-bd9e-a480202ab0112,737 cells
fbba1735-4c50-4cda-83e3-6e89cbf754631,957 cells
7743aab2-d4b0-4bd1-8d44-48559ff90f871,934 cells
80578aa0-0580-44fe-a6ec-e27b4d470c3f1,327 cells
frozen in liquid nitrogen30,969 cells
surgical resection30,969 cells
35.74,813 cells
34.54,482 cells
23.83,915 cells
40.93,755 cells
36.23,070 cells
44.12,979 cells
41.02,737 cells
39.21,957 cells
Unassigned1,934 cells
28.51,327 cells
Unassigned13,641 cells
202010,503 cells
20216,825 cells
mechanical dissociation,detergent solubilization30,969 cells
0.1% Tween-2030,969 cells
Ben-Gurion University of the Negev30,969 cells
ASPC 212,188 cells
VA111,599 cells
VA52,433 cells
ASPC 11,963 cells
ASPC 4799 cells
ASPC 3559 cells
VA3459 cells
VA2270 cells
VA8264 cells
VA6200 cells
VA4194 cells
VA741 cells
Unassigned23,086 cells
diabetes mellitus7,883 cells
ASPC15,509 cells
Adipocytes15,460 cells
10x 3' v3, single-nucleus30,969 cells
normal30,969 cells
female23,508 cells
male7,461 cells
visceral fat30,969 cells
Jewish Israeli16,968 cells
Arab8,152 cells
German3,915 cells
Unassigned1,934 cells
33 years7,552 cells
48 years4,813 cells
53 years3,915 cells
34 years3,755 cells
24 years2,979 cells
41 years2,737 cells
29 years1,957 cells
adult1,934 cells
28 years1,327 cells
30-3911,307 cells
40-497,550 cells
20-296,263 cells
50-593,915 cells
adult1,934 cells
Alias names
GSE281356