Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors
Summary: Bone, cartilage, and marrow adipocytes are generated by skeletal progenitors, but the relationships between lineages and mechanisms controlling their differentiation are poorly understood. We established mouse clonal skeletal progenitors with distinct differentiation properties and analyzed...
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doaj-6d8cc9c0a1914da9a5d8aec5e6615d092020-11-24T22:25:47ZengElsevierStem Cell Reports2213-67112018-07-01111212227Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal ProgenitorsMaria Rostovskaya0Samantha Donsante1Benedetto Sacchetti2Dimitra Alexopoulou3Sylvia Klemroth4Andreas Dahl5Mara Riminucci6Paolo Bianco7Konstantinos Anastassiadis8Stem Cell Engineering, BIOTEC, Technische Universität Dresden, 01307 Dresden, Germany; Corresponding authorDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyNGS Facility, BIOTEC, Technische Universität Dresden, 01307 Dresden, GermanyNGS Facility, BIOTEC, Technische Universität Dresden, 01307 Dresden, GermanyNGS Facility, BIOTEC, Technische Universität Dresden, 01307 Dresden, GermanyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyStem Cell Engineering, BIOTEC, Technische Universität Dresden, 01307 Dresden, Germany; Corresponding authorSummary: Bone, cartilage, and marrow adipocytes are generated by skeletal progenitors, but the relationships between lineages and mechanisms controlling their differentiation are poorly understood. We established mouse clonal skeletal progenitors with distinct differentiation properties and analyzed their transcriptome. Unipotent osteogenic and adipogenic cells expressed specific transcriptional programs, whereas bipotent clones combined expression of those genes and did not show a unique signature. We tested potential regulators of lineage commitment and found that in the presence of interferon-γ (IFNγ) adipogenic clones can be induced to osteogenesis and that their adipogenic capacity is inhibited. Analysis of IFNγ-regulated genes showed that lineage signatures and fate commitment of skeletal progenitors were controlled by EGR1 and EGR2. Knockdown experiments revealed that EGR1 is a positive regulator of the adipogenic transcriptional program and differentiation capacity, whereas EGR2 inhibits the osteogenic program and potency. Therefore, our work revealed transcriptional signatures of osteogenic and adipogenic lineages and mechanism triggering cell fate. : In this article, Rostovskaya and colleagues established clonal skeletal progenitors with distinct differentiation properties from mouse bone marrow. RNA-seq analysis revealed transcriptional signatures of osteogenic and adipogenic lineages and IFNγ signaling as potential regulator of cell fate commitment. IFNγ is a negative regulator of Egr1 and Egr2 transcription factors. Egr1 maintains adipogenic and Egr2 suppresses osteogenic transcriptional program and commitment. Keywords: bone marrow stromal cells, skeletal progenitors, lineage commitment, transcriptional signatures, interferon-γ signaling, Egr1/2 transcription factorshttp://www.sciencedirect.com/science/article/pii/S2213671118302327 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Rostovskaya Samantha Donsante Benedetto Sacchetti Dimitra Alexopoulou Sylvia Klemroth Andreas Dahl Mara Riminucci Paolo Bianco Konstantinos Anastassiadis |
spellingShingle |
Maria Rostovskaya Samantha Donsante Benedetto Sacchetti Dimitra Alexopoulou Sylvia Klemroth Andreas Dahl Mara Riminucci Paolo Bianco Konstantinos Anastassiadis Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors Stem Cell Reports |
author_facet |
Maria Rostovskaya Samantha Donsante Benedetto Sacchetti Dimitra Alexopoulou Sylvia Klemroth Andreas Dahl Mara Riminucci Paolo Bianco Konstantinos Anastassiadis |
author_sort |
Maria Rostovskaya |
title |
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors |
title_short |
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors |
title_full |
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors |
title_fullStr |
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors |
title_full_unstemmed |
Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors |
title_sort |
clonal analysis delineates transcriptional programs of osteogenic and adipogenic lineages of adult mouse skeletal progenitors |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2018-07-01 |
description |
Summary: Bone, cartilage, and marrow adipocytes are generated by skeletal progenitors, but the relationships between lineages and mechanisms controlling their differentiation are poorly understood. We established mouse clonal skeletal progenitors with distinct differentiation properties and analyzed their transcriptome. Unipotent osteogenic and adipogenic cells expressed specific transcriptional programs, whereas bipotent clones combined expression of those genes and did not show a unique signature. We tested potential regulators of lineage commitment and found that in the presence of interferon-γ (IFNγ) adipogenic clones can be induced to osteogenesis and that their adipogenic capacity is inhibited. Analysis of IFNγ-regulated genes showed that lineage signatures and fate commitment of skeletal progenitors were controlled by EGR1 and EGR2. Knockdown experiments revealed that EGR1 is a positive regulator of the adipogenic transcriptional program and differentiation capacity, whereas EGR2 inhibits the osteogenic program and potency. Therefore, our work revealed transcriptional signatures of osteogenic and adipogenic lineages and mechanism triggering cell fate. : In this article, Rostovskaya and colleagues established clonal skeletal progenitors with distinct differentiation properties from mouse bone marrow. RNA-seq analysis revealed transcriptional signatures of osteogenic and adipogenic lineages and IFNγ signaling as potential regulator of cell fate commitment. IFNγ is a negative regulator of Egr1 and Egr2 transcription factors. Egr1 maintains adipogenic and Egr2 suppresses osteogenic transcriptional program and commitment. Keywords: bone marrow stromal cells, skeletal progenitors, lineage commitment, transcriptional signatures, interferon-γ signaling, Egr1/2 transcription factors |
url |
http://www.sciencedirect.com/science/article/pii/S2213671118302327 |
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