Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Embryonic myeloid cells orchestrate niche cell homeostasis critical for the establishment of the definitive HSC pool [II]

ABSTRACT: The lifelong replenishment of blood cells relies on the function of definitive HSCs that migrate to the bone marrow during development. This process is tightly controlled by the bone marrow microenvironment. Embryonic macrophages emerge before the onset of definitive hematopoiesis, seed into discrete tissues and contribute to specialized resident macrophages throughout life. However, the functional impact of embryonic macrophages on HSCs or the niche remains unknown. Here, by taking advantage of a lineage tracer mouse tool we show that bone marrow macrophages consist of two ontogenetically distinct cell populations from embryonic and adult hematopoiesis. Mice lacking embryonic myeloid cells have decreased HSC numbers in the bone marrow accompanied by an increase of stem cells in the liver of neonate mice. The emergence of HSCs from embryonic sources is unperturbed because pre-HSC and HSC numbers are normal, suggesting a key role for embryo-derived myeloid cells in orchestrating HSC trafficking around birth. We show here that the establishment of a normal cellular niche space in the bone marrow critically depends on embryonic myeloid cells that are important for the development of mesenchymal stromal cells, but not other non-hematopoietic niche cells, providing evidence for a specific role for embryo-derived myeloid cells in the establishment of a normal niche environment pivotal for HSC homing.

ORGANISM(S): Mus musculus

PROVIDER: GSE265965 | GEO | 2024/05/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Embryonic myeloid cells orchestrate niche cell homeostasis critical for the establishment of the definitive HSC pool

Project description:The lifelong replenishment of blood cells relies on the function of definitive HSCs that migrate to the bone marrow during development. This process is tightly controlled by the bone marrow microenvironment. Embryonic macrophages emerge before the onset of definitive hematopoiesis, seed into discrete tissues and contribute to specialized resident macrophages throughout life. However, the functional impact of embryonic macrophages on HSCs or the niche remains unknown. Here, by taking advantage of a lineage tracer mouse tool we show that bone marrow macrophages consist of two ontogenetically distinct cell populations from embryonic and adult hematopoiesis. Mice lacking embryonic myeloid cells have decreased HSC numbers in the bone marrow accompanied by an increase of stem cells in the liver of neonate mice. The emergence of HSCs from embryonic sources is unperturbed because pre-HSC and HSC numbers are normal, suggesting a key role for embryo-derived myeloid cells in orchestrating HSC trafficking around birth. We show here that the establishment of a normal cellular niche space in the bone marrow critically depends on embryonic myeloid cells that are important for the development of mesenchymal stromal cells, but not other non-hematopoietic niche cells, providing evidence for a specific role for embryo-derived myeloid cells in the establishment of a normal niche environment pivotal for HSC homing.

2024-11-20 | GSE282288 | GEO

Embryonic myeloid cells orchestrate niche cell homeostasis critical for the establishment of the definitive HSC pool

2024-04-30 | GSE265827 | GEO

ICAM-1 deficiency in the bone marrow niche impairs quiescence and repopulation of hematopoietic stem cells

Project description:The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1-/-) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favors myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSCs quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche.

2018-06-21 | GSE114836 | GEO

Molecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffoldsMolecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffolds

Project description:Hematopoietic stem cell transplantation (HSCT) is successfully applied since the late 1950s, however, its efficacy still needs to be improved. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an advanced ex vivo culture system is needed that supports the proliferation and maintains the pluripotency of HSC to override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro and thus, to amplify high numbers of undifferentiated HSCs, we used an optimized HSC cell culture medium in combination with artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS). After 14 days in vitro (DIV) cell culture, we performed transcriptome and proteome analysis of the whole cell populations. Ingenuity pathway analysis (IPA) indicated that our 3D PDMS cell culture scaffolds activated interleukin, SREBP, mTOR and FOXO signaling pathways as well as the HSC metabolism, which we confirmed by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways and HSC metabolism are well known to promote the expansion HSCs and are involved in their pluripotency maintenance. After selection and enrichment of immature CD34-positive/CD38-negative HSCs using FACS sorting, we could confirm our findings by another proteome analysis followed by IPA. Thus, we could show that our 3D bone marrow-like PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSC efficiently ex vivo.

2021-11-10 | PXD025849 | Pride

Identification of a portal vessel-associated fetal liver hematopoietic stem cell niche

Project description:Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation. Characterization of the transcriptome of fetal liver and adult bone marrow niche using RNA-seq

2015-12-03 | E-GEOD-72341 | biostudies-arrayexpress

Mitochondrial activity dictates definitive hematopoietic stem cell production and lympho-myeloid lineage segregation during mouse embryogenesis [scRNAseq]

Project description:Mitochondrial metabolism determines bone marrow hematopoietic stem cell (HSC) heterogeneity, and influences long-term blood repopulation potential. However, when and how this mitochondrial regulation of definitive HSCs originates is unexplored. We show that dynamic changes in mitochondrial activity during endothelial to hematopoietic transition (EHT) drives the production of mature HSCs in the mouse embryo. Pharmacological and genetic manipulations show that reduced mitochondrial activity activates Wnt signalling to promote expansion of mature HSCs in the AGM. Further, single cell transcriptomics and functional assays uncovered mitochondrial membrane potential (MMP) driven functional heterogeneity within the mature HSC pool. MMPlow HSCs are myeloid-biased and exhibit enhanced differentiation potential. Contrarily, MMPhigh HSCs are lymphoid-biased with diminished differentiation potential. Mechanistically, low mitochondrial activity upregulates PI3K signalling to fuel embryonic HSC differentiation. We provide insights into the metabolic regulation of HSC origin and function, that can be leveraged to direct HSC fate decisions for clinical interventions.

2024-08-27 | GSE274538 | GEO

Isolation and functional characterization of the arteriole hematopoietic stem cell niche

Project description:Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM) that govern the delicate balance between HSC quiescence, self-renewal, and differentiation. It has been suggested that quiescent HSCs localize adjacent to BM arteriole endothelial cells in a significant and non-random distribution. This data suggests that the arteriole BM vascular niche may be the primary HSC niche. Because the BM arteriole niche is composed of tightly-associated pericytes, including smooth muscle actin+, LepR+, Nestin+, NG2+, and nonmyelinating Schwann cells, we sought to begin to uncouple the arteriole BM EC niche by examining its capacity to support the maintenance and expansion of HSCs ex vivo and in vivo. We developed a method to isolate and culture BM arteriole endothelial cells in serum-/growth factor-free conditions, allowing for a non-biased approach to examining their instructive function. Utilizing our protocol, we demonstrate that BM endothelial cells, but not BM stromal cells, have the capacity to expand long-term repopulating, multi-lineage HSCs in lieu of complex serum and cytokine supplementation. In addition, transplantation of arteriole endothelial cells promoted rapid hematopoietic recovery and protected HSCs following an LD50 dose of myeloablative irradiation. These data demonstrate that arteriole-derived BM endothelial cells are endowed with the necessary signals to support the self-renewal and regenerative capacity of LT-HSCs and that transplantation of arteriole BM endothelial cells could be used as a therapeutic means to decrease pancytopenias associated with myeloablative treatments to treat a wide array of disease states. Transcriptome sequencing of bone marrow endothelial cells and bone marrow stroma, in vitro and in vivo, with and without HSC co-culture.

2015-11-04 | E-GEOD-61636 | biostudies-arrayexpress

Igf2bp2 deletion reduces energy metabolism, gIgf2bp2 deletion reduces energy metabolism, growth signaling, and aging of hematopoietic stem cells in micerowth signaling, and aging of hematopoietic stem cells in mice

Project description:Increasing evidence links metabolic activity and cell growth to decline in hematopoietic stem cell (HSC) function during aging. The Lin28b/Hmga2 pathway controls tissue development and in the hematopoietic system the postnatal downregulation of this pathway causes a decrease in self renewal of adult HSCs compared to fetal HSCs. Igf2bp2 is an RNA binding protein and a mediator of the Lin28b/Hmga2 pathway, which regulates metabolism and growth signaling by influencing RNA stability and translation of its target genes. It is currently unknown whether Lin28/Hmga2/Igf2bp2 signaling impacts on aging-associated impairments in HSC function and hematopoiesis. Here, we analyzed homozygous Igf2bp2 germline knockout mice and wildtype control animals to address this question. The study shows that Igf2bp2 deletion rescues aging phenotypes of the hematopoietic system, such as the expansion of HSC numbers in bone marrow and the biased increase of myeloid cells in peripheral blood. This rescue of hematopoietic aging coincides with reduced mitochondrial metabolism and glycolysis in Igf2bp2-/- HSCs compared to Igf2bp2+/+ HSCs. Conversely, Igf2bp2 overexpression activates protein synthesis pathways in HSCs and leads to a rapid loss of self renewal by enhancing myeloid skewed differentiation in an mTOR/PI3K-dependent manner. Together, these results show that Igf2bp2 regulates energy metabolism and growth signaling in HSCs and that the activity of this pathways influences self renewal, differentiation, and aging of HSCs.

2024-05-21 | PXD018535 | Pride

Mitochondrial activity dictates definitive hematopoietic stem cell production and lympho-myeloid lineage segregation during mouse mouse embryogenesis [bulkRNAseq]

Project description:Mitochondrial metabolism determines bone marrow hematopoietic stem cell (HSC) heterogeneity, and influences long-term blood repopulation potential.Self-renewal and multilineage engraftment capacity of hematopoietic stem cells (HSCs) are key properties leveraged for their clinical use in bone marrow transplantation. Variations in long-term blood reconstitution ability are partly attributed to the functional heterogeneity in HSCs, which is influenced by the dynamic mitochondrial metabolic state, in addition to differences in gene expression. However, when and how this mitochondrial regulation of definitive HSCs originates is unexplored. Whether metabolic variation is an outcome of the diverse HSC milieu, or an inherent property of the emergent HSCs, is not known. Here, Wwe show that dynamic changes in mitochondrial activity during endothelial to hematopoietic transition (EHT) drives the production of mature HSCs in the mouse embryo. Pharmacological and genetic manipulations show that hematopoietic emergence during the endothelial to hematopoietic transition (EHT) in the aorta-gonad-mesonephros (AGM) region involves mitochondrial remodelling. reduced mitochondrial activity activates Wnt signalling to promote expansion of mature HSCs in the AGM. Further, single cell transcriptomics and functional assays uncovered mitochondrial membrane potential (MMP) driven functional heterogeneity within the mature HSC pool. MMPlow HSCs are myeloid-biased and exhibit enhanced differentiation potential. Contrarily, MMPhigh HSCs are lymphoid-biased with diminished differentiation potential. Mechanistically, low mitochondrial activity upregulates PI3K signalling to fuel embryonic HSC differentiation. We provide insights into the metabolic regulation of HSC origin and function, that can be leveraged to direct HSC fate decisions for clinical interventions.

2024-08-27 | GSE274537 | GEO

Vascular niche induction of hematopoietic progenitors from pluripotent stem cells

Project description:Pluripotent stem cells (PSC) represent an alternative source of hematopoietic stem cells (HSCs). Clinical translation is impeded by limited engraftment of human (h)PSC-multipotent progenitor cells (MPP). This barrier suggests that additional cues are required for definitive hematopoiesis. We hypothesized that vascular niche producing Notch ligands Jagged-1 (JAG1) and Delta-like ligand-4 (DLL4) would drive definitive hematopoiesis. To test our hypothesis, hes2 human embryonic stem cells (hESC) 2 and Macaca nemestrina (Mn) iPSC line-7 were differentiated with cytokines Â± endothelial cells (EC), which express JAG1 and DLL4. EC co-culture supported emergence of 8-fold more CD34+CD45+ cells compared to co-culture with cytokines Â± ECs with JAG1 or DLL4 knockdown. EC-induced cells exhibit Notch activation and express HSC-specific targets of Notch signaling RUNX1 and GATA2. EC-induced PSC-MPP engraft at a higher level in NSG mice compared to cytokine-induced cells (10% >5 months), and selection increased engraftment (30%). Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction is similar to levels achieved for cord blood MPP and up to 20-fold higher than hPSC-MPP engraftment. Our findings identify a previously underappreciated role for endothelial Notch ligands in PSC definitive hematopoiesis and production of long-term engrafting CD34+ cells and suggest they are critical for HSC emergence. Transcriptome sequencing of Macaca nemestrina (Mn) iPSCs

2015-12-31 | E-GEOD-64644 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data