Universität zu Köln

Mizikova, Ivana ORCID: 0000-0002-3440-9133, Lesage, Flore, Cyr-Depauw, Chanele, Cook, David P., Hurskainen, Maria ORCID: 0000-0003-1818-0647, Hanninen, Satu M., Vadivel, Arul, Bardin, Pauline, Zhong, Shumei, Carpen, Olli, Vanderhyden, Barbara C. and Thebaud, Bernard (2022). Single-Cell RNA Sequencing-Based Characterization of Resident Lung Mesenchymal Stromal Cells in Bronchopulmonary Dysplasia. Stem Cells, 40 (5). S. 479 - 493. OXFORD: OXFORD UNIV PRESS. ISSN 1549-4918

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Abstract

Late lung development is a period of alveolar and microvascular formation, which is pivotal in ensuring sufficient and effective gas exchange. Defects in late lung development manifest in premature infants as a chronic lung disease named bronchopulmonary dysplasia (BPD). Numerous studies demonstrated the therapeutic properties of exogenous bone marrow and umbilical cord-derived mesenchymal stromal cells (MSCs) in experimental BPD. However, very little is known regarding the regenerative capacity of resident lung MSCs (L-MSCs) during normal development and in BPD. In this study we aimed to characterize the L-MSC population in homeostasis and upon injury. We used single-cell RNA sequencing (scRNA-seq) to profile in situ Ly6a(+) L-MSCs in the lungs of normal and O-2-exposed neonatal mice (a well-established model to mimic BPD) at 3 developmental timepoints (postnatal days 3, 7, and 14). Hyperoxia exposure increased the number and altered the expression profile of L-MSCs, particularly by increasing the expression of multiple pro-inflammatory, pro-fibrotic, and anti-angiogenic genes. In order to identify potential changes induced in the L-MSCs transcriptome by storage and culture, we profiled 15 000 Ly6a(+) L-MSCs after in vitro culture. We observed great differences in expression profiles of in situ and cultured L-MSCs, particularly those derived from healthy lungs. Additionally, we have identified the location of Ly6a(+)/Col14a1(+) L-MSCs in the developing lung and propose Serpinf1 as a novel, culture-stable marker of L-MSCs. Finally, cell communication analysis suggests inflammatory signals from immune and endothelial cells as main drivers of hyperoxia-induced changes in L-MSCs transcriptome.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mizikova, Ivana UNSPECIFIED orcid.org/0000-0002-3440-9133 UNSPECIFIED Lesage, Flore UNSPECIFIED UNSPECIFIED UNSPECIFIED Cyr-Depauw, Chanele UNSPECIFIED UNSPECIFIED UNSPECIFIED Cook, David P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hurskainen, Maria UNSPECIFIED orcid.org/0000-0003-1818-0647 UNSPECIFIED Hanninen, Satu M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vadivel, Arul UNSPECIFIED UNSPECIFIED UNSPECIFIED Bardin, Pauline UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhong, Shumei UNSPECIFIED UNSPECIFIED UNSPECIFIED Carpen, Olli UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanderhyden, Barbara C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thebaud, Bernard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-688057
DOI:	10.1093/stmcls/sxab023
Journal or Publication Title:	Stem Cells
Volume:	40
Number:	5
Page Range:	S. 479 - 493
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1549-4918
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIUM-DERIVED FACTOR; STEM-CELLS; GENE-EXPRESSION; MATRIX METALLOPROTEINASE-1; TISSUE INHIBITORS; PROGENITOR CELLS; SOLUBLE ICAM-1; POTENTIAL ROLE; LONG-TERM; PRETERM Multiple languages Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68805