Similar Datasets
Project description:We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection.
2024-02-29 | GSE240914 | GEO
Project description:We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection.
2024-02-29 | GSE240913 | GEO
Project description:We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection.
2024-02-29 | GSE240912 | GEO
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis
| PRJNA1005679 | ENA
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [scATAC-seq]
| PRJNA1005686 | ENA
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [scRNA-seq]
| PRJNA1005683 | ENA
Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [Bulk RNA-seq]
| PRJNA1005684 | ENA
Project description:Neonates are highly susceptible to inflammation and infection. Here, we investigate how late fetal liver (FL) mouse hematopoietic stem and progenitor cells (HSPCs) respond to inflammation, testing the hypothesis that deficits in the engagement of emergency myelopoiesis (EM) pathways limit neutrophil output and contribute to perinatal neutropenia. We show that fetal HSPCs have limited production of myeloid cells at steady state and fail to activate a classical adult-like EM transcriptional program. Moreover, we find that fetal HSPCs can respond to EM-inducing inflammatory stimuli in vitro but are restricted by maternal anti-inflammatory factors, primarily interleukin-10 (IL-10), from activating EM pathways in utero. Accordingly, we demonstrate that the loss of maternal IL-10 restores EM activation in fetal HSPCs but at the cost of fetal demise. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus unresponsive to EM activation signals and susceptible to infection.
| S-EPMC10954379 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-11 | GSE252549 | GEO
Project description:In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production is observed, often mediated by the pro-inflammatory cytokine IFN-γ. IL-10 inhibits IFN-γ secretion, largely by its effects on macrophages and dendritic cells, but, paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work we used different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-γ transcriptional signature, and we show that IFN-γ mediates IL-10-driven EM. We also found that IL-10, unexpectedly, induces IFN-γ production by all T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening new perspectives for the design of IL-10-based immunotherapies.
2021-10-13 | GSE172060 | GEO