Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rondini, Elizabeth A., Ramseyer, Vanesa D., Burl, Rayanne B., Pique-Regi, Roger, Granneman, James G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
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
_version_ 1783742038934552576
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
work_keys_str_mv AT rondinielizabetha singlecellfunctionalgenomicsrevealsplasticityofsubcutaneouswhiteadiposetissuewatduringearlypostnataldevelopment
AT ramseyervanesad singlecellfunctionalgenomicsrevealsplasticityofsubcutaneouswhiteadiposetissuewatduringearlypostnataldevelopment
AT burlrayanneb singlecellfunctionalgenomicsrevealsplasticityofsubcutaneouswhiteadiposetissuewatduringearlypostnataldevelopment
AT piqueregiroger singlecellfunctionalgenomicsrevealsplasticityofsubcutaneouswhiteadiposetissuewatduringearlypostnataldevelopment
AT grannemanjamesg singlecellfunctionalgenomicsrevealsplasticityofsubcutaneouswhiteadiposetissuewatduringearlypostnataldevelopment