Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lyl-1 links primitive macrophages and microglia development to neuropsychiatric disorders

ABSTRACT: The regulation of developmental haematopoiesis by the bHLH transcription factor Lyl-1 has been the focus of our present study. Analysing how Lyl-1 may impact mouse developmental haematopoiesis indicated that Lyl-1 marks YS-derived primitive macrophage progenitors, as well as embryonic microglia. During ontogeny, microglia which representtissue macrophages of the central nervous system emerge from haematopoietic stem cell-independent progenitors originating from the yolk sac (YS). Activation of microglia during development is often critical and my lead to neuropsychiatric diseases in the adult. Here, we show that Lyl-1 disruption alters the development of microglia with far reaching consequences. Lyl-1-deficiency leads to decreased dendritic spine density and impaired neuronal activity, as well as impaired social interactions with increased anxiety-like behaviour. We thus identify Lyl-1 as a critical regulator of primitive macrophage and microglia development, whose disruption impacts microglia development and functionality, leading to a distinct neuropsychiatric phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE128378 | GEO | 2025/03/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Project description: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.

2020-12-31 | E-MTAB-9618 | biostudies-arrayexpress

The role of the yolk sac in human fetal development and identification of a hepatocyte-like cell in the human yolk sac (SS2)

Project description:The human yolk sac (YS) is an extra-embryonic tissue critical for early prenatal life development. It is the first site of haematopoiesis where progenitors differentiate from endoderm within blood islands of the yolk sac contributing initially to primitive erythropoiesis and in subsequent waves to erythro-myeloid and lymphoid differentiation.

2023-03-01 | E-MTAB-10888 | biostudies-arrayexpress

The role of the yolk sac in human fetal development and identification of a hepatocyte-like cell in the human yolk sac

2023-03-01 | E-MTAB-10552 | biostudies-arrayexpress

Meningeal lymphatics-microglia axis regulates synaptic physiology [egfp/vegfc]

Project description:Microglia are thought to originate exclusively from primitive macrophage progenitors in the yolk sac (YS) and persist throughout life without contributions from definitive hematopoiesis. Here, using Ms4a3-Cre lineage tracing, pharmacological manipulation, and RNA-sequencing, we elucidated the presence and unique features of monocyte-derived macrophages (MDMs) in the brain parenchyma at baseline and during microglia repopulation. Using parabiosis and skull transplantation, we show that MDMs derived from both peripheral blood and skull bone marrow can repopulate microglia-depleted brains, and they display distinct transcriptional profiles compared to YS-derived microglia. Blood-derived macrophages possess a disease-associated microglia (DAM)-like phenotype, while skull-derived macrophages mirror injury-responsive microglia (IRM) and exhibit significant interactions with T cells. Repetitive microglia depletion and subsequent MDM engraftment in 5xFAD mice led to increased amyloid burden, suggesting differential responses of resident microglia and MDMs towards amyloid pathology. Our results reveal the heterogeneous origins and functions of microglia during cell turnover and neurodegeneration, offering insights that may guide microglia-targeted immunomodulatory strategies for neurological disorders.

2025-03-21 | GSE285072 | GEO

Induced pluripotent stem cell-derived primitive macrophages as a cellular platform to model tissue-resident macrophage differentiation and function

Project description:Specialized tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that migrate into developing tissues and terminally differentiate in situ. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMac) can terminally differentiate into specialized macrophages using growth factors and organ-specific cues. Co-culturing murine iMac with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMac differentiated in vivo into microglia following injection into the brain, and functional alveolar macrophages after engraftment in the lung.

2017-07-20 | GSE99078 | GEO

HLA-DR is absent in primitive macrophages through epigenetic silencing of master regulator CIITA

Project description:The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.

2023-08-01 | GSE210868 | GEO

Lyl-1 links primitive macrophages and microglia development to neuropsychiatric disorders

Project description:Lyl-1 links primitive macrophages and microglia development to neuropsychiatric disorders

| PRJNA527292 | ENA

The T-box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors [scRNA-Seq]

Project description:Extra-embryonic mesoderm (ExM), the earliest cells that traverse through the primitive streak, give rise to the endothelium as well as hematopoietic progenitors in the developing yolk-sac (YS). How a specific subset of ExM becomes committed to a hematopoietic fate remains unclear. Here we report that Eomesodermin (Eomes), a T-box transcription factor, is transiently expressed in ExM progenitors that generate virtually all YS hematopoietic and endothelial cells. Using an embryonic stem cell (ESC) differentiation system, we find that Eomes activity is essential for the production of primitive erythrocytes and for the normal development of Runx1+ HE that generates the definitive hematopoietic progenitors. RNA-Seq and ATAC-Seq experiments reveal that Eomes governs the accessibility of numerous hematopoietic enhancers that SCL normally utilizes to specify primitive erythrocytes and HE in Flk-1hi/PdgfRa- hematovascular mesoderm. ChIP-seq experiments suggest that Eomes coordinates the development of hemogenic competent mesoderm in the context of Activin/Nodal and Tead-Yap signaling. Finally, single-cell- RNA-seq (scRNAseq) shows that in the absence of Eomes function diversion towards an endothelial rather than hematopoietic fate occurs after the initial specification of Flk-1+/SCL+ hematovascular mesoderm. Collectively, these experiments demonstrate that Eomes sits at the top of the transcriptional hierarchy, functioning upstream of Runx1 expression and SCL functional activity, and promotes hemogenic competence of the entire YS mesodermal lineage.

2020-11-01 | GSE140061 | GEO

The T-box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors [ChIP-Seq]

2020-11-01 | GSE140000 | GEO

The T-box Transcription Factor Eomesodermin Governs Hemogenic Competence of Yolk Sac Mesodermal Progenitors [ATAC-Seq]

2020-11-01 | GSE139998 | GEO