Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq analysis of gene expression in macrophages progenitors from the yolk sac of murine embryos at embryonic days 9 and 10, and the modifications resulting from a defective expression of the transcription factor Lyl-1

ABSTRACT: Most resident macrophages (MF) populations in adult tissues arise from MF progenitors populations that emerge during ontogeny, either from haematopoietic stem cells (HSC), or from Yolk Sac (YS) progenitors produced prior to HSC development. The YS generates two populations of MF progenitors. In the earliest one, called primitive, MF progenitors arise from monopotent/uni-lineage progenitors, while in the second one they derive from multipotent erythro-myeloid progenitors. These two populations soon mix in the blood circulation, and as they are highly similar in phenotype, the specific features and function of the two MF progenitors populations are still unclear. When investigating the function of the bHLH transcription factor Lyl-1 during the development of blood cells in mouse embryos, we observed that Lyl-1 expression marks YS primitive MF progenitors. Lyl-1 bHLH disruption leads to an increased production and a defective differentiation of primitive MF progenitors. To gain a better insight into primitive MF progenitors specificity and function, we performed a RNA-seq analysis of these progenitors sorted from the YS at embryonic day (E) 9, when the YS only contains primitive MF progenitors, and at E10, when it contains both primitive MF progenitors and those produced by erythro-myeloid progenitors. At both stages, MF progenitors were collected from the YS of either wild-type or Lyl-1-deficient embryos, to better understand the role of Lyl-1 in the development of Lyl-1-expressing resident macrophage populations.

INSTRUMENT(S): Agilent 2100 Bioanalyzer, Cell Sorter Aria III or Influx (BD biosciences), Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Isabelle Godin

PROVIDER: E-MTAB-9618 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Filarial nematodes are arthropod-borne nematodes that cause a variety of economically important diseases such as onchocerciasis (river blindness), lymphatic filariasis, and heartworm disease. The most widespread filarial disease of humans is lymphatic filariasis, caused by worms in the genera Wuchereria and Brugia. Lymphatic filariasis is an economic and social burden in endemic countries and affects approximately 119 million people worldwide (Michael, 1997). In humans, the worms live in and block the lymph vessels, causing improper flow of lymph, and inflammation of the lymphatic system. The symptoms are fever, swollen limbs and genitals, generalized malaise, and can progress to a debilitating condition known as elephantiasis This research focuses on the transmission of these worms to the disseminating mosquito host, and it is based on the interesting observation that mf must be at least 7 days old to successfully infect the mosquito (de Hollanda, 1982). Newborn mf that have not â??maturedâ?? cannot successfully penetrate the midgut of the mosquito, and subsequently cannot develop to the L3 stage (Fuhrman, 1987). Previous work done by another group 20 years ago suggests that the molecular makeup of the worm surface changes during this maturation process (Furman, 1983 a and b). We used microarray analysis to characterize changes in gene expression that take place during the mf maturation process. Understanding the gene expression changes that occur as the mf mature will allow us to understand the nature of the philological transition that allows mf to move from the human to the mosquito host. With this information in hand, we can eventually identify parasite molecules that could be targeted to either stop parasite reproduction or prevent transmission of the mf to the mosquito. This would stop parasite transmission in endemic areas. Brugia pahangi mature mf (30 days and older) RNA was compared to immature mf (3 days and younger). Three biological replicates were performed each with two technical replicates

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RNA-seq analysis of gene expression in macrophages progenitors from the yolk sac of murine embryos at embryonic days 9 and 10, and the modifications resulting from a defective expression of the transcription factor Lyl-1

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