TATTOO-seq delineates spatial and cell type-specific regulatory programs in the developing limb

The coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we developed and applied an unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs underlying the emergence of specialized cell types during mouse limb development and their spatial integration. We identify multiple transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, suggesting two parallel yet highly interconnected regulatory systems.We demonstrate that the embryonic limb undergoes a complex multiscale reorganization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, alterations of preexisting cell states' molecular identities, and changes in their relative spatial distribution. Our study shows how multidimensional single-cell, spatially resolved molecular atlases can allow the deconvolution of spatial identity and cell fate and reveal the interconnected genetic networks that regulate organogenesis and its reorganization upon genetic alterations

A Mouse Model of Acrodermatitis Enteropathica: Loss of Intestine Zinc Transporter ZIP4 (Slc39a4) Disrupts the Stem Cell Niche and Intestine Integrity

Loss-of-function of the zinc transporter ZIP4 in the mouse intestine mimics the lethal human disease acrodermatitis enteropathica. This is a rare disease in humans that is not well understood. Our studies demonstrate the paramount importance of ZIP4 in the intestine in this disease and reveal that a root cause of lethality is disruption of the intestine stem cell niche and impaired function of the small intestine. This, in turn, leads to dramatic weight loss and death unless treated with exogenous zinc

Les déterminants de la perscription de clonazépam dans la douleur neuropathique (une étude qualitative auprès de 21 médecins généraliste en Hérault)

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice.

Catch-up growth after insults to growing organs is paramount to achieving robust body proportions. In fly larvae, injury to individual tissues is followed by local and systemic compensatory mechanisms that allow the damaged tissue to regain normal proportions with other tissues. In vertebrates, local catch-up growth has been described after transient reduction of bone growth, but the underlying cellular responses are controversial. We developed an approach to study catch-up growth in foetal mice in which mosaic expression of the cell cycle suppressor p21 is induced in the cartilage cells (chondrocytes) that drive long-bone elongation. By specifically targeting p21 expression to left hindlimb chondrocytes, the right limb serves as an internal control. Unexpectedly, left-right limb symmetry remained normal, revealing deployment of compensatory mechanisms. Above a certain threshold of insult, an orchestrated response was triggered involving local enhancement of bone growth and systemic growth reduction that ensured that body proportions were maintained. The local response entailed hyperproliferation of spared left limb chondrocytes that was associated with reduced chondrocyte density. The systemic effect involved impaired placental function and IGF signalling, revealing bone-placenta communication. Therefore, vertebrates, like invertebrates, can mount coordinated local and systemic responses to developmental insults that ensure that normal body proportions are maintained

Do relocated villages experience more forest cover change? Resettlements, shifting cultivation and forests in the Lao PDR

This study explores the relationships between forest cover change and the village resettlement and land planning policies implemented in Laos, which have led to the relocation of remote and dispersed populations into clustered villages with easier access to state services and market facilities. We used the Global Forest Cover Change (2000–2012) and the most recent Lao Agricultural Census (2011) datasets to assess forest cover change in resettled and non-resettled villages throughout the country. We also reviewed a set of six case studies and performed an original case study in two villages of Luang Prabang province with 55 households, inquiring about relocation, land losses and intensification options. Our results show that resettled villages have greater baseline forest cover and total forest loss than most villages in Laos but not significant forest loss relative to that baseline. Resettled villages are consistently associated with forested areas, minority groups, and intermediate accessibility. The case studies highlight that resettlement coupled with land use planning does not necessarily lead to the abandonment of shifting cultivation or affect forest loss but lead to a re-spatialization of land use. This includes clustering of forest clearings, which might lead to fallow shortening and land degradation while limited intensification options exist in the resettled villages. This study provides a contribution to studying relationships between migration, forest cover change, livelihood strategies, land governance and agricultural practices in tropical forest environments

Evaluation of somatic hybrids of potato with Solanum stenotomum after a long-term in vitro conservation

International audienc

TATTOO-seq delineates spatial and cell type-specific regulatory programs during limb patterning

The coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we applied a new unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs that underlie the emergence of specialized cell types during limb development and their integration in space. We uncovered combinations of transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, enabling the deconvolution of cell fate and position identity. We demonstrate that the embryonic limb undergoes a complex multi-scale re-organization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, specific alterations in the molecular identities of other pre-existing cell states and changes in their relative spatial distribution. Altogether, our study shows how multi-dimensional single-cell and spatially resolved molecular atlases could reveal the interconnected genetic networks that regulate the intricacies of organogenesis and its reorganization upon genetic alterations

TATTOO-seq delineates spatial and cell type–specific regulatory programs in the developing limb

International audienceThe coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we developed and applied an unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs underlying the emergence of specialized cell types during mouse limb development and their spatial integration. We identify multiple transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, suggesting two parallel yet highly interconnected regulatory systems. We demonstrate that the embryonic limb undergoes a complex multiscale reorganization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, alterations of preexisting cell states’ molecular identities, and changes in their relative spatial distribution. Our study shows how multidimensional single-cell, spatially resolved molecular atlases can allow the deconvolution of spatial identity and cell fate and reveal the interconnected genetic networks that regulate organogenesis and its reorganization upon genetic alterations

Mosaic local proliferation blockade in chondrocytes of the left limb results in systemic growth reduction.

<p>(A) Right femur and tibia length (normalized to the average <i>ePit-p21</i> littermate) from E17.5 embryos treated with Dox (<i>n =</i> 4 <i>ePit-p21</i> and <i>n</i> = 11 <i>ePit-Col-p21</i>) or untreated (<i>n =</i> 5 and <i>n</i> = 6). Comparison by 2-way ANOVA with Genotype and Bone identity as variables. <i>p-</i>Values for Genotypes are shown below graphs; <i>p-</i>values for Sidak’s post hoc test shown on graph. (B–C) Box and whisker plots for normalized bone length (panel B) and weight (panel C) of <i>ePit-Col-p21</i> and <i>Col2a1-rtTA; Igs7</i>^{<i>TRE-tdT/+</i>} embryos (<i>eCol-tdT</i>, expressing tdT in all cartilage elements), compared to their controls (<i>ePit-p21</i> and <i>ePit-tdT</i>) by unpaired <i>t</i> tests. <i>p-</i>Values corrected for multiple comparisons (Holm-Sidak method) are shown. For panel B, <i>n =</i> 22 <i>ePit-p21</i>, <i>n</i> = 26 <i>ePit-Col-p21</i>, <i>n</i> = 25 <i>ePit-tdT</i>, and <i>n</i> = 5 <i>eCol-tdT</i>). For panel C, <i>n =</i> 4, 11, 24, and 5. (D) Model of the systemic growth response after local chondrocyte arrest triggers a stress signal. (E–F) qRT-PCR (panel E) and in situ hybridisation (panel F) for the indicated transcripts in the proliferative plus pre-hypertrophic zone from <i>ePit-Col-p21</i> embryos. Panel E shows one of 2 independent experiments with 3 distinct biological replicates each (total <i>n</i> = 6). The –ΔCt (relative to <i>Gapdh</i>) for each stress-related transcript was compared by a paired <i>t</i> test (left versus right). In panel F, <i>n =</i> 2 E15.5, <i>n</i> = 4 E16.5, and <i>n</i> = 6 E17.5 embryos (arrowheads denote <i>Il6</i> expression). For panel A–C and E, see also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005086#pbio.2005086.s003" target="_blank">S3 Data</a>. Dox, doxycycline; E, embryonic day; qRT-PCR, quantitative real-time polymerase chain reaction; tdT, tdTomato.</p

Mosaic proliferation blockade in the left limb cartilage slightly reduces bone growth but not left–right limb symmetry.

<p>(A) Absolute length of the indicated left bones of <i>ePit-p21</i> (<i>n =</i> 4–7 depending on the bone) and <i>ePit-Col-p21</i> (<i>n =</i> 11–15) E17.5 embryos. (B, C) Skeletal preparations (panel B) and quantification of the left/right ratio (panel C, mean ± SD) of the calcified region of the indicated bones at E17.5 (<i>n =</i> 4–7 <i>ePit-p21</i> and <i>n</i> = 11–15 <i>ePit-Col-p21</i> mice, depending on the bone) and P0 (<i>n =</i> 5–9, and 6–9). Dashed lines in panel B mark the ends of the mineralized region in control bones. In panel A and C, data were analysed by 2-way ANOVA with Genotype and Bone identity as variables. <i>p-</i>Values are shown below the graphs. For variables with significantly different measurements, Sidak’s post hoc test <i>p-</i>values are shown in the graph. For panel A and C, see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2005086#pbio.2005086.s003" target="_blank">S3 Data</a>. E, embryonic day; P, postnatal day.</p