Single-cell atlas of major haematopoietic tissues in the mouse embryo
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161933 | GEO | 2020/11/21
REPOSITORIES: GEO
Similar Datasets
Project description:Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of Ezh2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMP). Ezh2 activity is critical at the onset of the endothelial-to-hematopoietic transition generating EMPs but rapidly dispensable after that. We identified a lack of downregulation of Wnt signaling as the primary reason in the generation of non-functional EMPs. Together, our findings demonstrate a critical and specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.
2021-08-16 | GSE150032 | GEO
Project description:Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of Ezh2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMP). Ezh2 activity is critical at the onset of the endothelial-to-hematopoietic transition generating EMPs but rapidly dispensable after that. We identified a lack of downregulation of Wnt signaling as the primary reason in the generation of non-functional EMPs. Together, our findings demonstrate a critical and specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.
2021-08-16 | GSE181869 | GEO
Project description:Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of Ezh2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMP). Ezh2 activity is critical at the onset of the endothelial-to-hematopoietic transition generating EMPs but rapidly dispensable after that. We identified a lack of downregulation of Wnt signaling as the primary reason in the generation of non-functional EMPs. Together, our findings demonstrate a critical and specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.
2021-06-01 | GSE150292 | GEO
Project description:Hematopoietic stem cells (HSCs) are derived from hemogenic endothelial cells (HECs) during embryogenesis. The HSC-primed HECs are peak at embryonic day (E) 10 and have been efficiently captured by the marker combination CD41-CD43-CD45-CD31+CD201+Kit+CD44+ (PK44) in the aorta-gonad-mesonephros (AGM) region of mouse embryos most recently. In the present study, we investigated the spatiotemporal and functional heterogeneity of PK44 cells around the time of emergence of HSCs. First, PK44 cells in E10 AGM region could be further divided into three molecularly different populations showing endothelial- or hematopoietic-biased characteristics. Specifically, with the combination of Kit, the expression of CD93 or CD146 could divide PK44 cells into endothelial- and hematopoietic-feature biased populations, which was further functionally validated at single cell level. Next, PK44 population could also be detected in the yolk sac, showing a developmental dynamics and functional diversification similar to those in the AGM region. Importantly, PK44 cells in the yolk sac demonstrated an unambiguous multi-lineage reconstitution capacity after in vitro incubation. Regardless of the functional similarity, PK44 cells in the yolk sac displayed transcriptional features different to those in the AGM region. Taken together, our work delineated the spatiotemporal characteristics of HECs represented by PK44, and revealed a previously unknown HSC competence of HECs in the yolk sac. These findings provided a fundamental basis for in-depth studying the different origins and molecular programs of HSC generation in the future.
2021-08-20 | GSE173833 | GEO
Project description:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We use human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human yolk-sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of yolk sac-like primitive erythropoiesis, but no yolk sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a yolk sac-like SOX17- haemogenic endothelial intermediate.
2020-11-11 | GSE124085 | GEO
Project description:The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We use human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human yolk-sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of yolk sac-like primitive erythropoiesis, but no yolk sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1/1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data defines the hierarchical requirements for both RUNX1 and GFI1/1B during early human haematopoiesis arising from a yolk sac-like SOX17- haemogenic endothelial intermediate.
2020-11-11 | GSE124084 | GEO
Project description:Hematopoiesis occurs in distinct waves. ‘Definitive’ hematopoietic stem cells (HSC) with the potential for all blood lineages emerge in the aorta-gonado-mesonephros (AGM), while ‘primitive’ progenitors, whose potential is thought to be limited to erythrocytes, megakaryocytes and macrophages (MΦ), arise earlier in the yolk sac (YS). Here, we questioned whether other YS lineages exist that have not been identified, partially owing to limitations of current lineage tracing models. We established the use of Cdh5CreERT2 for hematopoietic fate mapping, which revealed the YS origin of mast cells (MC). YS derived MC are replaced by definitive MC, which maintain themselves independently from the BM in the adult. Replacement occurs with tissue specific kinetics. MC in the skin, but not other organs, remain largely YS derived prenatally and are phenotypically and transcriptomically distinct from definite adult MC. We conclude that dual hematopoietic origin is not MΦ specific, but shared between these two myeloid lineages.
2018-06-01 | GSE104790 | GEO
Project description:Hoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non- Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations.
2019-01-07 | GSE124710 | GEO
Project description:Hematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial, and hematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a hemogenic organ akin to the dorsal aorta. Here, we examined the hemogenic activity of the developing endocardium. Mouse heart explants generated myeloid and erythroid colonies in the absence of circulation. Hemogenic activity arose from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and was transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, were expressed in and required for the hemogenic activity of the endocardium. Together, these data suggest that a subset of endocardial and yolk sac endothelial cells expressing cardiac markers serve as a de novo source for transient definitive hematopoietic progenitors. Two independent biological duplicates of freshly isolated mouse tissues (caudal half, heart tube, yolk sac) were sorted for CD31+/CD41-/CD45- cells.
2013-08-17 | E-GEOD-40260 | biostudies-arrayexpress
Project description:Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive. We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation. By single-cell RNA sequencing (sc-RNA seq), we trace the developmental origins of immune dysregulation in a mouse model of idiopathic autism. It is found that both in aorta-gonad-mesonephros (AGM) and yolk sac (YS) progenitors, the dysregulation of HDAC1-mediated epigenetic machinery alters definitive hematopoiesis during embryogenesis and downregulates the expression of the AP-1 complex for microglia development. Subsequently, these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain. We further confirm that dysregulated immune profiles are associated with specific microbiota composition, which may serve as a biomarker to identify autism of immune-dysregulated subtypes. Our findings elucidate a shared mechanism for the origin of immune dysregulation from the brain to the gut in autism and provide new insight to dissecting the heterogeneity of autism, as well as the therapeutic potential of targeting immune-dysregulated autism subtypes.
2022-05-09 | GSE197618 | GEO