Biology subjects

Orsenigo, R.

Publications and source records attributed to Orsenigo, R..

2 recordsLinked to original sources

bioRxiv2024

Hemogenic endothelium of the vitelline and umbilical arteries is the major contributor to mouse fetal lympho-myelopoiesis

Embryonic hematopoiesis consists of distinct waves originating in rapid succession from different anatomical locations. Hematopoietic progenitors appearing earlier than definitive hematopoietic stem cells (HSCs) play key roles in fetal and postnatal life. However, their precise origin, identity and the extent of their contribution need further clarification. To this aim, we took advantage of a genetic fate-mapping strategy in mice that allows labeling and tracking of distinct subsets of hemogenic endothelium (HE). Time-course labeling of hematopoietic progenitors emerging from HE between E8.5 and E9.5, before intra-embryonic definitive HSC generation, revealed a major fetal lympho-myeloid contribution which declined in the adult. Lineage tracing coupled with whole-mount imaging and single-cell RNA sequencing located its source within hematopoietic clusters of vitelline and umbilical arteries. Functional assays confirmed the transient nature of these progenitors. We therefore unveiled a hitherto unidentified early wave of fetal-restricted hematopoietic stem/progenitor cells poised for differentiation that provide a major contribution to pre-natal hematopoiesis.

developmental biology↗

bioRxiv2024

Loss of Lkb1 cooperates with BrafV600E and UV radiation increasing melanoma multiplicity and neural-like dedifferentiation

The mechanisms cooperating with BRAFV600E oncogene in addition to ultraviolet (UV) radiation in melanoma development are of great interest. Analysis of human melanoma tumors (TCGA) indicates that 50% or more of the samples express no or low amounts of LKB1 protein. Here, we report that the concomitant neonatal BrafV600E activation and Lkb1 tumor suppressor ablation in melanocytes led to full melanoma development. A postnatal single-dose of UVB radiation had no effect on melanoma onset in Lkb1-depleted mice in respect to BrafV600E-irradiated mice, but increased tumor multiplicity. In agreement to this and previous reports, Lkb1 null irradiated mice showed a deficient DNA damage repair (DDR). Histologically, tumors lacking Lkb1 were enriched in neural-like tumor morphology. Genetic profiling and gene set enrichment analyses of tumor samples-mutated genes indicated that loss of Lkb1 promoted the selection of altered genes associated to neural differentiation processes. Thus, these results suggest that loss of Lkb1 cooperates with BrafV600E and UVR impairing DDR and increasing melanoma multiplicity and neural-like dedifferentiation.

cancer biology↗