Biology subjects

Mailhe, M.-P.

Publications and source records attributed to Mailhe, M.-P..

6 recordsLinked to original sources

bioRxiv2025

Distinct origin and fate for fetal hematopoietic progenitors

It was proposed that two sequential sources of intraembryonic multipotent progenitors ensure blood cell production from late gestation into adulthood, with only the latter producing self-renewing hematopoietic stem cells (HSC). How these two populations differ and how they impact the establishment of the postnatal immune system, remains poorly understood. Using complementary lineage tracing models, we showed that the first emerging embryonic multipotent progenitors (eMPP) are responsible for late gestation hematopoiesis. They are distinct from HSC that do not significantly contribute to embryonic mature blood cells. eMPP are the predominant source of embryonic lymphocytes and lymphoid tissue inducer cells, some of which persist for life. Between E12.5 and E16.5 eMPP rapidly differentiate, whereas HSC expand 20-fold. Altogether, these results support the notion that eMPP establish the embryonic adaptive immune system and shape the lymphoid organs where later adaptive immune responses occur, while HSC expand to sustain blood cell production throughout life.

developmental biology↗

bioRxiv2023

Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine. A high-definition imaging dataset analyzed using a deep-learning based pipeline allowed the unambiguous identification of hematopoietic and stromal populations, and enabled determining a neighboring network composition, at the single cell resolution. Throughout active hematopoiesis, progenitors preferentially associate with hepatoblasts, but not with stellate or endothelial cells. We found that, unlike yolk sac-derived progenitors, intra-embryonic progenitors respond to a chemokine gradient created by CXCL12-producing stellate cells. These results revealed that FL hematopoiesis is a spatiotemporal dynamic process, defined by an environment characterized by low cytokine concentrations.

developmental biology↗

bioRxiv2022

Single cell atlas of Xenoturbella bocki highlights the limited cell-type complexity of a non-vertebrate deuterostome lineage

Evidence for a sister relationship between Xenacoelomorpha and Ambulacraria (Xenambulacraria) has revived the longstanding debate surrounding the complexity of the Urdeuterostomian and Urbilaterian ancestors and has led to a reassessment of early bilaterian features. Employing whole organism single-cell RNA-seq in the marine xenacoelomorph worm Xenoturbella bocki, we show that Xenambulacrarian nerve nets share regulatory features and a peptidergic identity with those found in cnidarians and protostomes. We also suggest that Xenacoelomorpha muscles are likely to have evolved their "smooth" phenotype convergently. Furthermore, we identify pigmented cells as a potential synapomorphy of the Xenambulacraria. Taken together, these data are consistent with a simplification from an ancestral urbilaterian/urdeuterostomian body plan and a non-centralized nerve net, minimally differentiated contractile cells and evidence of deuterostome cell-type synapomorphies.

evolutionary biology↗

bioRxiv2021

Identification of fetal liver stromal subsets in spectral cytometry using the parameter autofluorescence

The fetal liver is the main hematopoietic organ during embryonic development. The fetal liver is also the unique anatomical site where hematopoietic stem cells expand before colonizing the bone marrow, where they ensure life-long blood cell production and become mostly resting. The identification of the different cell types that comprise the hematopoietic stroma in the fetal liver is essential to understand the signals required for the expansion and differentiation of the hematopoietic stem cells. We used a panel of monoclonal antibodies to identify fetal liver stromal cells in a 5-laser equipped spectral flow cytometry analyzer. The "Autofluorescence Finder" of SONY ID7000 software identified two distinct autofluorescence emission spectra. Using autofluorescence as a fluorescence parameter we could assign the two autofluorescent signals to three distinct cell types and identified surface markers that characterize these populations. We found that one autofluorescent population corresponds to hepatoblasts and cholangiocytes whereas the other expresses mesenchymal transcripts and was identified as stellate cells. Importantly, after birth, autofluorescence becomes the unique identifying property of hepatoblasts because mature cholangiocytes are no longer autofluorescent. These results show that autofluorescence used as a parameter in spectral flow cytometry is a useful tool to identify new cell subsets that are difficult to analyze in conventional flow cytometry.

developmental biology↗

bioRxiv2021

Myeloid and endothelial cells cooperate to promote hematopoietic stem cells expansion in the fetal niche.

During embryonic development, very few hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium, that will be expanded in a very specific niche. This fetal HSC niche comprises a complex and dynamic molecular network of interactions between multiple cell types, including endothelial cells (ECs) and mesenchymal stromal cells. It is known that functional changes in the hematopoietic niche, such as aging, vascular cell remodelling or inflammation can directly affect HSCs. Among all these inflammatory regulators, the eicosanoid prostaglandin E (PGE2) has been shown to be very important during embryonic life. However, the precise source of PGE2 in the embryo is still elusive. Here we show that all the genes involved in PGE2 synthesis and transport are expressed by distinct cells of the caudal hematopoietic tissue (CHT) in the zebrafish embryo and in the mouse fetal liver, suggesting that each cell type acts sequentially and collaboratively with the others to produce PGE2 and ultimately expand HSCs. Among these cells, we found myeloid cells (both neutrophils and macrophages) to be absolutely necessary, as they concur to the production of PGH2, the precursor of PGE2. To measure the impact of myeloid cells, we generated a genetic model of myeloid ablation, which caused a loss of HSCs in the CHT, that could be rescued by supplementing zebrafish embryos with PGE2 or PGH2. ECs expressed the slco2b1 transporter to import PGH2, and ptges3, the necessary enzyme to convert this latter into PGE2. Taken altogether, our data show that the triad composed of neutrophils, macrophages and ECs concurs to HSC expansion in the CHT.

developmental biology↗

bioRxiv2017

Cnidarian cell type diversity revealed by whole-organism single-cell RNA-seq analysis

A hallmark of animal evolution is the emergence and diversification of cell type-specific transcriptional states. But systematic and unbiased characterization of differentiated gene regulatory programs was so far limited to specific tissues in a few model species. Here, we perform whole-organism single cell transcriptomics to map cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal that display complex tissue-level bodyplan organization. We uncover high diversity of transcriptional states in Nematostella, demonstrating cell type-specific expression for 35% of the genes and 51% of the transcription factors (TFs) detected. We identify eight broad cell clusters corresponding to cell classes such as neurons, muscles, cnidocytes, or digestive cells. These clusters comprise multiple cell modules expressing diverse and specific markers, uncovering in particular a rich repertoire of cells associated with neuronal markers. TF expression and sequence analysis defines the combinatorial code that underlies this cell-specific expression. It also reveals the existence of a complex regulatory lexicon of TF binding motifs encoded at both enhancer and promoters of Nematostella tissue-specific genes. Whole organism single cell RNA-seq is thereby established as a tool for comprehensive study of genome regulation and cell type evolution.

genomics↗