Biology subjects

Dechamps, N.

Publications and source records attributed to Dechamps, N..

5 recordsLinked to original sources

bioRxiv2026

Transplantation in neonate mouse recipients enhances umbilical cord blood CD34+ cells permissiveness to ETO2::GLIS2-driven transformation

Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive pediatric acute myeloid leukemia subtype, frequently driven by the ETO2::GLIS2 (EG) gene fusion in de novo AMKL patients. The EG fusion confers poor prognosis and high relapse risk. In a previous study, we demonstrated that human fetal hematopoietic cells are intrinsically permissive to EG-driven transformation and that microenvironmental cues critically enhance leukemogenesis in less permissive human cord blood (CB) cells. However, most pediatric AML models are established in adult recipient mice, potentially overlooking developmental niche-specific effects. Here, we investigated whether mouse neonates provide a more permissive environment for EG-driven leukemogenesis from human CB hematopoietic stem and progenitor cells (HSPCs). Comparison of xenotransplants of EG-transduced CB CD34+ cells into sublethally irradiated NSG neonate or adult mice show that neonatal recipients are more supportive of EG-driven leukemia when cell doses are adjusted for recipient size. Neonates exhibited a higher frequency of leukemia-initiating cells (LIC), enhanced expansion of EG/GFP+ leukemic cells, and increased disease penetrance compared with adults at similar dose/size ratio, despite similar overall human hematopoietic engraftment. Leukemic cells arising in neonates and adults displayed comparable phenotypes and secondary transplantation capacities, indicating functional equivalence. Both CD34+CD38- and CD34+CD38+ CB subpopulations were sensitive to EG-driven transformation, with neonates consistently showing higher LIC frequencies than adults. Together, our findings demonstrate that the developmental stage of the host microenvironment is a critical extrinsic determinant of EG-mediated leukemogenesis. Neonatal recipients constitute a physiologically relevant and highly sensitive model for studying pediatric AMKL initiation with low cell inputs, enabling refined investigation of microenvironmental signals that promote leukemia development and may reveal novel therapeutic vulnerabilities

cancer biology↗

bioRxiv2024

Humanized in vivo bone marrow models orchestrate multi-lineage human hematopoietic cell development

Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate differentiation and preservation of hematopoietic stem/progenitor cells (HSPCs). Although murine BM has been extensively analyzed, the human BM microenvironment remains less understood. Immune-deficient murine models have enabled the analysis of molecular and cellular regulation of human HSPCs, which remains limited as human hematopoietic cells develop in xenogenic microenvironments. In this study, we thoroughly characterized a humanized (h) in vivo BM model, based on mesenchymal stromal cell (MSC) differentiation (called hOssicles (hOss)), and hematopoietic cell compartments generated 3 months post-transplant of CD34+ cells using single-cell RNA sequencing and cellular barcoding. Serial isolation of MSCs and HSPCs from hOss and transplant experiments revealed the dynamic nature of these hBM niches. hOss altered human hematopoietic development by modulating myeloid/lymphoid cell production and HSPC levels. Clonal tracking highlighted hematopoietic cell cross-talks between the murine BM and hOss, indicating the multipotent or more restricted lineage origin of human hematopoiesis shared in the BM sites.

cell biology↗

bioRxiv2023

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans.

Testicular cancer is an increasing burden in modern societies and the most common malignancy among young adult males. Environment contaminants, especially endocrine disrupting compounds (EDC), may play a significant role in the development of these cancers through epigenetic alterations occurring during fetal and neonatal development. As long-term studies in humans and suitable experimental models with the potential to develop testicular cancer are lacking, no causal link can be established between endocrine disruptor exposure and testicular cancer incidence. Therefore, we developed an experimental model that recapitulates the differentiation of germ cells from primordial germ cells (pluripotency) into spermatocytes (meiosis) by using xenografted human fetal testis combined with germ cell transplantation into adult testis compartments. Using this model, we demonstrate that long-term fetal exposure (until 12 weeks) to a mixture of Di-2-ethylhexylphthalate (DEHP) and Bisphenol A (BPA), two most prevalent plasticizers, could interfere with fetal germ cell differentiation, leading to carcinogenesis and seminomas. Transcriptome, methylome, and histological analyses reveal that BPA/DEHP exposure induced some significant hallmarks of germ cell tumors to occur: persistent pluripotent and proliferative germ cells, global hypomethylation of CpGs in germ cells, abnormal expression of meiotic markers and fibrotic signatures in fetal testis. Additionally, we found that EDC-exposed fetal germ cells were more likely to develop seminoma in a context that allows spermatogenesis to begin. This study proposes the first experimental evidence that EDC exposure can cause long-term, irreversible lesions in fetal germ cells, which then lead to testicular tumorigenesis in adults.

cancer biology↗

bioRxiv2023

Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.

genomics↗

bioRxiv2022

Loss of CD24 promotes radiation- and chemo-resistance by inducing stemness properties associated with a hybrid E/M state in breast cancer cells

There is compelling evidence that cancer stem cells (CSCs) play an essential role in failure of conventional antitumor therapy. In breast cancer, CD24-/low/CD44+ phenotype as well as a high aldehyde dehydrogenase activity (ALDH+) are widely associated with CSC subtypes. Furthermore, CD24-/low/CD44+ pattern is also characteristic of the mesenchymal cells generated by an epithelial-mesenchymal transition (EMT). CD24 is a surface marker expressed in many tumor types, however, its biological functions and role in cancer progression and treatment resistance remain poorly documented. We have previously shown that loss of CD24 expression in breast cancer cells is associated with radiation resistance, in relationship with the control of oxidative stress. Because ROS are known to mediate the effects of anticancer drugs as well as ionizing radiation, we investigated if CD24 could be defined as an actor of both radiation- and chemo-resistance of breast cancer cells. Using the HMLE breast cancer cell model, we observed that loss of CD24 expression induces stemness properties associated with the acquisition of a hybrid E/M phenotype. The CD24-/low cells were intrinsically more resistant than CD24+ cells. The resistance was linked to a lower level of ROS, and CD24 controlled ROS levels through the regulation of mitochondrial functions independently of antioxidant activity. Together, these results suggest a key role of CD24 in de-differentiation process of breast cancer cells, promoting acquisition of therapeutic resistance properties.

cancer biology↗