4.7 Article

Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

Journal

STEM CELL RESEARCH & THERAPY
Volume 8, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s13287-017-0701-4

Keywords

Single cell sequencing; Human adipose tissue; Adipocyte progenitor; Mesenchymal stem cells

Funding

  1. Swedish Research Council
  2. Novo Nordisk Foundation
  3. Tripartite Immuno-metabolism Consortium (TrIC) [NNF15CC0018486]
  4. MSAM consortium [NNF15SA0018346]
  5. Swedish Diabetes Foundation
  6. Stockholm County Council
  7. Diabetes Research Program at Karolinska Institutet
  8. European Foundation for the Study of Diabetes [Lilly 2014_5] Funding Source: researchfish
  9. Novo Nordisk Fonden [NNF15SA0018346, NNF15OC0015894, NNF15SA0018486, NNF14OC0010187] Funding Source: researchfish

Ask authors/readers for more resources

Regulation of adipose tissue stem cells (ASCs) and adipogenesis impact the development of excess body fat-related metabolic complications. Animal studies have suggested the presence of distinct subtypes of ASCs with different differentiation properties. In addition, ASCs are becoming the biggest source of mesenchymal stem cells used in therapies, which requires deep characterization. Using unbiased single cell transcriptomics we aimed to characterize ASC populations in human subcutaneous white adipose tissue (scWAT). The transcriptomes of 574 single cells from the WAT total stroma vascular fraction (SVF) of four healthy women were analyzed by clustering and t-distributed stochastic neighbor embedding visualization. The identified cell populations were then mapped to cell types present in WAT using data from gene expression microarray profiling of flow cytometry-sorted SVF. Cells clustered into four distinct populations: three adipose tissue-resident macrophage subtypes and one large, homogeneous population of ASCs. While pseudotemporal ordering analysis indicated that the ASCs were in slightly different differentiation stages, the differences in gene expression were small and could not distinguish distinct ASC subtypes. Altogether, in healthy individuals, ASCs seem to constitute a single homogeneous cell population that cannot be subdivided by single cell transcriptomics, suggesting a common origin for human adipocytes in scWAT.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Nutrition & Dietetics

The impact of dietary fatty acids on human adipose tissue

Paul Petrus, Peter Arner

PROCEEDINGS OF THE NUTRITION SOCIETY (2020)

Article Endocrinology & Metabolism

Influence of Aging and Menstrual Status on Subcutaneous Fat Cell Lipolysis

Mikael Ryden, Hui Gao, Peter Arner

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2020)

Article Medicine, General & Internal

Cellular heterogeneity and microenvironmental control of skin cancer

B. M. Lichtenberger, M. Kasper

Summary: Healthy tissues contain cells with cancer-causing mutations, but the immediate environment of these mutant cells greatly influences their potential for malignancy. Understanding the cellular heterogeneity and interactions in health and disease is crucial for developing new cancer therapies.

JOURNAL OF INTERNAL MEDICINE (2021)

Article Endocrinology & Metabolism

Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance

Regine A. Jersin, Divya Sri Priyanka Tallapragada, Andre Madsen, Linn Skartveit, Even Fjaere, Adrian McCann, Laurence Dyer, Aron Willems, Jan-Inge Bjune, Mona S. Bjune, Villy Vage, Hans Jorgen Nielsen, Havard Luong Thorsen, Bjorn Gunnar Nedrebo, Christian Busch, Vidar M. Steen, Matthias Blueher, Peter Jacobson, Per-Arne Svensson, Johan Ferno, Mikael Ryden, Peter Arner, Ottar Nygard, Melina Claussnitzer, Stale Ellingsen, Lise Madsen, Jorn V. Sagen, Gunnar Mellgren, Simon N. Dankel

Summary: This study reveals that the small neutral amino acid transporter SLC7A10 plays a significant role in regulating adipocyte resilience to nutrient and oxidative stress, reducing reactive oxygen species generation and lipid accumulation, and improving mitochondrial respiration, ultimately leading to decreased adipocyte hypertrophy, insulin resistance, and type 2 diabetes.

DIABETES (2021)

Article Oncology

A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation

Yuan-Hung Lo, Kevin S. Kolahi, Yuhong Du, Chiung-Ying Chang, Andrey Krokhotin, Ajay Nair, Walter D. Sobba, Kasper Karlsson, Sunny J. Jones, Teri A. Longacre, Amanda T. Mah, Bahar Tercan, Alexandra Sockell, Hang Xu, Jose A. Seoane, Jin Chen, Ilya Shmulevich, Jonathan S. Weissman, Christina Curtis, Andrea Califano, Haian Fu, Gerald R. Crabtree, Calvin J. Kuo

Summary: Mutations in ARID1A are common in human cancer, but the oncogenic consequences of these mutations remain unclear. Using CRISPR/Cas9, researchers induced dysplasia, tumorigenicity, and mucinous differentiation in human gastric organoids, providing insights into the pathways affected by ARID1A mutation. Further analysis showed vulnerability of ARID1A-deficient organoids to inhibition of BIRC5/survivin, highlighting this pathway as crucial for early-stage gastric tumorigenesis.

CANCER DISCOVERY (2021)

Article Biology

LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

Carl Herdenberg, Pascal M. Mutie, Ola Billing, Ahmad Abdullah, Rona J. Strawbridge, Ingrid Dahlman, Simon Tuck, Camilla Holmlund, Peter Arner, Roger Henriksson, Paul W. Franks, Hakan Hedman

Summary: Herdenberg et al. demonstrate that adipogenesis and BMP signaling are disrupted in mouse cells lacking LRIG (Leucine-rich repeats and immunoglobulin-like domains) proteins. They also show that mutant LRIG/sma-10 variant worms exhibit defects in lipid storage and human LRIG1 variants are linked to higher body mass index while protecting against type 2 diabetes. This study suggests a conserved role of LRIG proteins in lipid metabolism and BMP signaling across different species.

COMMUNICATIONS BIOLOGY (2021)

Review Endocrinology & Metabolism

Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics

Pauline Morigny, Jeremie Boucher, Peter Arner, Dominique Langin

Summary: White adipocyte metabolism plays a crucial role in systemic metabolism regulation and is often disrupted in conditions like cancer and type 2 diabetes mellitus. This review provides an overview of lipid metabolism in white adipocytes and discusses how these pathways can serve as therapeutic targets in metabolic disorders.

NATURE REVIEWS ENDOCRINOLOGY (2021)

Article Biochemical Research Methods

Transcriptional bursts explain autosomal random monoallelic expression and affect allelic imbalance

Anton J. M. Larsson, Christoph Ziegenhain, Michael Hagemann-Jensen, Bjorn Reinius, Tina Jacob, Tim Dalessandri, Gert-Jan Hendriks, Maria Kasper, Rickard Sandberg

Summary: This study investigates the relationship between monoallelic gene expression and transcriptional bursting based on single-cell RNA analysis, demonstrating that transcriptional bursting process can explain the amount of monoallelic expression. The burst frequency largely determines the frequency of monoallelic observations, while the burst size has minimal impact on monoallelic observations. The findings reinforce the idea that studies of allelic imbalance can be affected by the inherent noise in transcriptional bursting.

PLOS COMPUTATIONAL BIOLOGY (2021)

Article Endocrinology & Metabolism

Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State

Enrichetta Mileti, Kelvin H. M. Kwok, Daniel P. Andersson, Anthony Mathelier, Amitha Raman, Jesper Backdahl, Jutta Jalkanen, Lucas Massier, Anders Thorell, Hui Gao, Peter Arner, Niklas Mejhert, Carsten O. Daub, Mikael Ryden

Summary: Selective hepatic insulin resistance is a feature of obesity and type 2 diabetes. This study showed that white adipose tissue in obese individuals also displays a selective insulin response, which is normalized by weight loss in most genes.

DIABETES (2021)

Article Endocrinology & Metabolism

An RNAi Screening of Clinically Relevant Transcription Factors Regulating Human Adipogenesis and Adipocyte Metabolism

Christel Bjork, Narmadha Subramanian, Jianping Liu, Juan Ramon Acosta, Beatriz Tavira, Anders B. Eriksson, Peter Arner, Jurga Laurencikiene

Summary: This study conducted a comprehensive analysis of TFs affected by metabolic conditions in human WAT, revealing their significant roles in adipogenesis and identifying JARID2 as a crucial TF. These findings provide important insights into the understanding of adipocyte generation and adipose tissue expansion.

ENDOCRINOLOGY (2021)

Article Cell Biology

Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer

Katie Cockburn, Karl Annusver, David G. Gonzalez, Smirthy Ganesan, Kailin R. Mesa, Kyogo Kawaguchi, Maria Kasper, Valentina Greco

Summary: In the adult epidermis of the skin, there are molecularly heterogeneous subpopulations within the stem cell compartment. These subpopulations undergo a series of transcriptional changes to gradually differentiate into terminally differentiated cells.

NATURE CELL BIOLOGY (2022)

Article Multidisciplinary Sciences

Injury prevents Ras mutant cell expansion in mosaic skin

Sara Gallini, Karl Annusver, Nur-Taz Rahman, David G. Gonzalez, Sangwon Yun, Catherine Matte-Martone, Tianchi Xin, Elizabeth Lathrop, Kathleen C. Suozzi, Maria Kasper, Valentina Greco

Summary: Healthy skin consists of a mixture of wild-type and mutant clones. After injury, wild-type cells suppress the abnormal growth induced by mutant Ras cells through the activation of the EGFR pathway. This injury-induced switch in competitive balance prevents the expansion of oncogenic mutant cells.

NATURE (2023)

Article Multidisciplinary Sciences

ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors

Oliver J. Mainwaring, Holger Weishaupt, Miao Zhao, Gabriela Rosen, Anna Borgenvik, Laura Breinschmid, Annemieke D. Verbaan, Stacey Richardson, Dean Thompson, Steven C. Clifford, Rebecca M. Hill, Karl Annusver, Anders Sundstrom, Karl O. Holmberg, Maria Kasper, Sonja Hutter, Fredrik J. Swartling

Summary: In this study, a transgenic mouse model of Group 3 medulloblastoma was generated by MYC overexpression, and it was shown that MYC suppresses ARF to drive tumorigenesis. Computational models and clinical data were used to identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. CDKN2A loss and p53 mutations were rare in MYC-driven Group 3 medulloblastomas.

NATURE COMMUNICATIONS (2023)

Meeting Abstract Oncology

A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and non-essential modes of oncogenic transformation.

Yuan-Hung Lo, Kevin S. Kolahi, Yuhong Du, Chiung-Ying Chang, Andrey Krokhotin, Ajay Nair, Walter D. Sobba, Kasper Karlsson, Sunny J. Jones, Teri A. Longacre, Amanda T. Mah, Alexandra Sockell, Jose A. Seoane, Jin Chen, Jonathan S. Weissman, Christina Curtis, Andrea Califano, Haian Fu, Gerald R. Crabtree, Calvin J. Kuo

CANCER RESEARCH (2021)

Correction Endocrinology & Metabolism

Genome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort (vol 34, pg 85, 2020)

Agne Kulyte, Veroniqa Lundback, Cecilia M. Lindgren, Jian'an Luan, Luca A. Lotta, Claudia Langenberg, Peter Arner, Rona J. Strawbridge, Ingrid Dahlman

MOLECULAR METABOLISM (2020)

No Data Available