Biology subjects

Duprez, D.

Publications and source records attributed to Duprez, D..

7 recordsLinked to original sources

bioRxiv2026

Maternal hyperglycemia impairs postnatal skeletal muscle growth and induces stage-dependent gene expression changes in mouse offspring

Maternal hyperglycemia can affect offspring development and metabolism, but how its effects on skeletal muscle change during postnatal life remains unclear. We investigated skeletal muscle phenotypes in male offspring of streptozotocin-induced hyperglycemic mice at 4 and 8 weeks of age, representing early post-weaning and later postnatal stages, respectively. Maternal hyperglycemia resulted in lower offspring body and skeletal muscle weights at both time points. Myofiber cross-sectional area was reduced without a reduction in total myofiber number, indicating impaired myofiber growth rather than myofiber loss. At 4 weeks, skeletal muscle showed type I/IIA hybrid myofibers and increased expression of fetal, myogenic, and proliferation-associated genes. This immature profile was not maintained at 8 weeks; instead, the transcriptional profile shifted toward reduced mitochondrial and oxidative metabolism. DNA methylation changes at 4 weeks showed limited correspondence with transcriptional alterations. Taken together, maternal hyperglycemia impaired postnatal myofiber growth at both time points, with distinct molecular profiles at 4 and 8 weeks.

physiology↗

bioRxiv2022

CXCR7 promotes foetal myoblast fusion at muscle fiber tips independently of Myomaker via a beta1integrin-EGFR-dependent mechanism

Muscle growth must be tightly regulated during development in order to obtain the final muscle shape. Myoblast fusion is a critical step of muscle growth, driving the formation of syncytial myofibers attaching at both ends to tendons. We investigated the role of the CXCR7 chemokine receptor in foetal muscle growth during chicken limb development. We show that CXCR7 displays a regionalized expression at the tips of myofibers close to tendons in foetal limb muscles, which is exclusive to the central location of the fusion gene MYOMAKER (TMEM8C in chicken) in foetal muscles. CXCR7 promotes myoblast fusion independently of TMEM8C in chicken limb muscles and in foetal myoblast cultures and requires EGF receptor signalling. The CXCR7 ligand, CXCL12, expressed in connective tissue, increases {beta}1integrin activation at the myotendinous junction and CXCR7 expression at muscle tips, resulting in a fusion promoting effect independent from a direct binding of CXCL12 to CXCR7 receptor. Our results evidence a CXCR7-dependent/TMEM8C-independent fusion mechanism at the myofiber tips that regulates muscle growth at the tendon/muscle interface during foetal myogenesis.

developmental biology↗

bioRxiv2019

Mechanical and molecular parameters that influence the tendon differentiation potential of C3H10T1/2 cells in 2D- and 3D-culture systems

One of the main challenges in tendon field relies in the understanding of regulators of the tendon differentiation program. The optimum culture conditions that favor tendon cell differentiation are not identified. Mesenchymal stem cells present the ability to differentiate into multiple lineages in cultures under different cues ranging from chemical treatment to physical constraints. We analyzed the tendon differentiation potential of C3H10T1/2 cells, a murine cell line of mesenchymal stem cells, upon different 2D- and 3D-culture conditions. We observed that C3H10T1/2 cells cultured in 2D conditions on silicone substrate were more prone to tendon differentiation assessed with the expression of the tendon markers Scx, Col1a1 and Tnmd as compared to cells cultured on plastic substrate. 3D fibrin environment was more favorable for Scx and Col1a1 expression compared to 2D-cultures. We also identified TGF{beta}2 as a negative regulator of Tnmd expression in C3H10T1/2 cells in 2D- and 3D-cultures. Altogether, our results provide us with a better understanding of the culture conditions that promote tendon gene expression and identify mechanical and molecular parameters on which we could play to define the optimum culture conditions that favor tenogenic differentiation in mesenchymal stem cells.

developmental biology↗

bioRxiv2018

In addition to being a marker for muscle connective tissue, Odd skipped-related 2 (OSR2) is expressed in differentiated muscle cells during chick development

The zinc finger transcription factor, Odd skipped-related 2 (OSR2) is a recognized marker of connective tissue in chick embryos. OSR2 gain- and loss-of-function experiments indicate a role in irregular connective tissue differentiation in chick limb undifferentiated cells. Re-investigation of OSR2 transcript location during chick development with in situ hybridization experiments showed that OSR2 was also expressed in differentiated muscle cells in limbs and head. OSR2 expression was also observed in differentiated myotubes in chick foetal myoblast cultures. This shows that in addition to being a marker of connective tissue, OSR2 is also expressed in muscle fibres during chick development.

developmental biology↗

bioRxiv2017

Genome-wide strategies identify molecular niches regulated by connective tissue-associated transcription factors

BackgroundConnective tissues support, connect and separate tissues and organs, playing crucial roles in development, homeostasis and fibrosis. Cell specification and differentiation is triggered by the activity of specific transcription factors. While key transcription factors have been identified for differentiation processes of most tissues, connective tissue differentiation remains largely unstudied.\n\nResultsTo gain insight into the regulatory cascades involved in connective tissue differentiation, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in the differentiation of mesenchymal cells into connective tissue subtypes. We combined RNA-seq with ChIP-seq profiling in chick limb cells following overexpression of individual transcription factors. We identified a set of common genes regulated by all five transcription factors, which constitutes a connective tissue core expression set. This common core was enriched in genes associated with axon guidance and myofibroblast signature. In addition, each of the transcription factors regulated a different set of extracellular matrix components and signalling molecules, which define local molecular niches important for connective tissue development and function.\n\nConclusionsThe established regulatory network identifies common and distinct molecular signatures downstream of five connective tissue-associated transcription factors and provides insight into the signalling pathways governing limb connective tissue differentiation. It also suggests a concept whereby local molecular niches can be created via the expression of specific transcription factors impinging on the specification of microenvironments.

developmental biology↗

bioRxiv2017

A dual transcript-discovery approach to improve the delimitation of gene features from RNA-seq data in the chicken model

The sequence of the chicken genome, like several other draft genome sequences, is presently not fully covered. Gaps, contigs assigned with low confidence and uncharacterized chromosomes result in gene fragmentation and imprecise gene annotation. Transcript abundance estimation from RNA sequencing (RNA-seq) data relies on read quality, library complexity and expression normalization. In addition, the quality of the genome sequence used to map sequencing reads and the gene annotation that defines gene features must also be taken into account. Partially covered genome sequence causes the loss of sequencing reads from the mapping step, while an inaccurate definition of gene features induces imprecise read counts from the assignment step. Both steps can significantly bias interpretation of RNA-seq data. Here, we describe a dual transcript-discovery approach combining a genome-guided gene prediction and a de novo transcriptome assembly. This dual approach enabled us to increase the assignment rate of RNA-seq data by nearly 20% as compared to when using only the chicken reference annotation, contributing therefore to a more accurate estimation of transcript abundance. More generally, this strategy could be applied to any organism with partial genome sequence and/or lacking a manually-curated reference annotation in order to improve the accuracy of gene expression studies.

bioinformatics↗

bioRxiv2017

Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in mice

Beige adipocyte differentiation within white adipose tissue, referred to as browning, is seen as a possible mechanism for increasing energy expenditure. The molecular regulation underlying the thermogenic browning process has not been entirely elucidated. Here, we identify the zinc finger transcription factor EGR1 as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes browning in the absence of external stimulation and activates Ucp1 that encodes the key thermogenic mitochondrial uncoupling protein-1. Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in subcutaneous inguinal white adipose tissue. Transcriptomic analysis of subcutaneous inguinal white adipose tissue in the absence of Egr1 identifies the molecular signature of white adipocyte browning downstream of Egr1 deletion and highlights a concomitant increase of beige differentiation marker and decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige adipocyte differentiation, while increasing extracellular matrix production. These results uncover the role of Egr1 in blocking energy expenditure via direct Ucp1 transcription regulation and highlight Egr1 as a therapeutic target for counteracting obesity.

developmental biology↗