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Single-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity

Alfred K. Ramirez, Simon N. Dankel, Bashir Rastegarpanah, Weikang Cai, Ruidan Xue, Mark Crovella, Yu-Hua Tseng, C. Ronald Kahn () and Simon Kasif ()
Additional contact information
Alfred K. Ramirez: Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
Simon N. Dankel: Hormone Laboratory, Haukeland University Hospital
Bashir Rastegarpanah: Department of Computer Science, Boston University
Weikang Cai: Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
Ruidan Xue: Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
Mark Crovella: Department of Computer Science, Boston University
Yu-Hua Tseng: Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
C. Ronald Kahn: Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
Simon Kasif: Boston University

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract White adipose tissue plays an important role in physiological homeostasis and metabolic disease. Different fat depots have distinct metabolic and inflammatory profiles and are differentially associated with disease risk. It is unclear whether these differences are intrinsic to the pre-differentiated stage. Using single-cell RNA sequencing, a unique network methodology and a data integration technique, we predict metabolic phenotypes in differentiating cells. Single-cell RNA-seq profiles of human preadipocytes during adipogenesis in vitro identifies at least two distinct classes of subcutaneous white adipocytes. These differences in gene expression are separate from the process of browning and beiging. Using a systems biology approach, we identify a new network of zinc-finger proteins that are expressed in one class of preadipocytes and is potentially involved in regulating adipogenesis. Our findings gain a deeper understanding of both the heterogeneity of white adipocytes and their link to normal metabolism and disease.

Date: 2020
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DOI: 10.1038/s41467-020-16019-9

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