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Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development
OBJECTIVE: The current study addresses the cellular complexity and plasticity of subcutaneous (inguinal) white adipose tissue (iWAT) in mice during the critical periods of perinatal growth and establishment. METHODS: We performed a large-scale single cell transcriptomic (scRNA-seq) and epigenomic (s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385178/ https://www.ncbi.nlm.nih.gov/pubmed/34298199 http://dx.doi.org/10.1016/j.molmet.2021.101307 |
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author | Rondini, Elizabeth A. Ramseyer, Vanesa D. Burl, Rayanne B. Pique-Regi, Roger Granneman, James G. |
author_facet | Rondini, Elizabeth A. Ramseyer, Vanesa D. Burl, Rayanne B. Pique-Regi, Roger Granneman, James G. |
author_sort | Rondini, Elizabeth A. |
collection | PubMed |
description | OBJECTIVE: The current study addresses the cellular complexity and plasticity of subcutaneous (inguinal) white adipose tissue (iWAT) in mice during the critical periods of perinatal growth and establishment. METHODS: We performed a large-scale single cell transcriptomic (scRNA-seq) and epigenomic (snATAC-seq) characterization of cellular subtypes (adipose stromal cells (ASC) and adipocyte nuclei) during inguinal WAT (subcutaneous; iWAT) development in mice, capturing the early postnatal period (postnatal days (PND) 06 and 18) through adulthood (PND56). RESULTS: Perinatal and adult iWAT contain 3 major ASC subtypes that can be independently identified by RNA expression profiles and DNA transposase accessibility. Furthermore, the transcriptomes and enhancer landscapes of both ASC and adipocytes dynamically change during postnatal development. Perinatal ASC (PND06) are highly enriched for several imprinted genes (IGs; e.g., Mest, H19, Igf2) and extracellular matrix proteins whose expression then declines prior to weaning (PND18). By comparison, adult ASC (PND56) are more enriched for transcripts associated with immunoregulation, oxidative stress, and integrin signaling. Two clusters of mature adipocytes, identified through single nuclei RNA sequencing (snRNA-seq), were distinctive for proinflammatory/immune or metabolic gene expression patterns that became more transcriptionally diverse in adult animals. Single nuclei assay for transposase-accessible chromatin (snATAC-seq) revealed that differences in gene expression were associated with developmental changes in chromatin accessibility and predicted transcription factor motifs (e.g., Plagl1, Ar) in both stromal cells and adipocytes. CONCLUSIONS: Our data provide new insights into transcriptional and epigenomic signaling networks important during iWAT establishment at a single cell resolution, with important implications for the field of metabolic programming. |
format | Online Article Text |
id | pubmed-8385178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83851782021-08-30 Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development Rondini, Elizabeth A. Ramseyer, Vanesa D. Burl, Rayanne B. Pique-Regi, Roger Granneman, James G. Mol Metab Original Article OBJECTIVE: The current study addresses the cellular complexity and plasticity of subcutaneous (inguinal) white adipose tissue (iWAT) in mice during the critical periods of perinatal growth and establishment. METHODS: We performed a large-scale single cell transcriptomic (scRNA-seq) and epigenomic (snATAC-seq) characterization of cellular subtypes (adipose stromal cells (ASC) and adipocyte nuclei) during inguinal WAT (subcutaneous; iWAT) development in mice, capturing the early postnatal period (postnatal days (PND) 06 and 18) through adulthood (PND56). RESULTS: Perinatal and adult iWAT contain 3 major ASC subtypes that can be independently identified by RNA expression profiles and DNA transposase accessibility. Furthermore, the transcriptomes and enhancer landscapes of both ASC and adipocytes dynamically change during postnatal development. Perinatal ASC (PND06) are highly enriched for several imprinted genes (IGs; e.g., Mest, H19, Igf2) and extracellular matrix proteins whose expression then declines prior to weaning (PND18). By comparison, adult ASC (PND56) are more enriched for transcripts associated with immunoregulation, oxidative stress, and integrin signaling. Two clusters of mature adipocytes, identified through single nuclei RNA sequencing (snRNA-seq), were distinctive for proinflammatory/immune or metabolic gene expression patterns that became more transcriptionally diverse in adult animals. Single nuclei assay for transposase-accessible chromatin (snATAC-seq) revealed that differences in gene expression were associated with developmental changes in chromatin accessibility and predicted transcription factor motifs (e.g., Plagl1, Ar) in both stromal cells and adipocytes. CONCLUSIONS: Our data provide new insights into transcriptional and epigenomic signaling networks important during iWAT establishment at a single cell resolution, with important implications for the field of metabolic programming. Elsevier 2021-07-21 /pmc/articles/PMC8385178/ /pubmed/34298199 http://dx.doi.org/10.1016/j.molmet.2021.101307 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Rondini, Elizabeth A. Ramseyer, Vanesa D. Burl, Rayanne B. Pique-Regi, Roger Granneman, James G. Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development |
title | Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development |
title_full | Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development |
title_fullStr | Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development |
title_full_unstemmed | Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development |
title_short | Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development |
title_sort | single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (wat) during early postnatal development |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385178/ https://www.ncbi.nlm.nih.gov/pubmed/34298199 http://dx.doi.org/10.1016/j.molmet.2021.101307 |
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