Single-cell multiomics of human fetal hematopoiesis defines a developmental specific population and a fetal signature
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PROVIDER: PRJNA793904 | ENA |
REPOSITORIES: ENA
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Project description:Knowledge of human fetal blood development and how it differs from adult is highly relevant to our understanding of congenital blood and immune disorders and childhood leukemia, of which the latter can originate in utero. Blood formation occurs in waves that overlap in time and space adding to heterogeneity, which necessitates single-cell approaches. Here, a combined single cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (Cellular-Indexing-of-Transcriptomes-and-Epitopes-by-Sequencing) the molecular profile of established immunophenotypic gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs) such as CD90 and CD49F were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow (BM) dataset revealed that the HSC state was less frequent in FL, whereas cells with lympho-myeloid signature were more abundant. An erythro-myeloid primed multipotent progenitor cluster was identified, potentially representing a transient, fetal-specific population. Furthermore, differentially expressed genes between fetal and adult counterparts were specifically analyzed, and a fetal core signature identified. The core gene set could separate subgroups of Acute Lymphoblastic Leukemia (ALL) by age, suggesting that a fetal program may be partially retained in specific sub-groups of pediatric leukemia. Our detailed single-cell map presented herein emphasizes molecular and immunophenotypic differences between fetal and adult blood cells, of significance for future studies of pediatric leukemia and blood development in general.
2023-06-28 | GSE192966 | GEO
Project description:Knowledge of human fetal blood development and how it differs from adult blood is highly relevant to our understanding of congenital blood and immune disorders and childhood leukemia, of which the latter can originate in utero. Blood formation occurs in waves that overlap in time and space, adding to heterogeneity, which necessitates single-cell approaches. Here, a combined single-cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), the molecular profile of established immunophenotype-gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs), such as CD90 and CD49F, were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow data set revealed that the HSC state was less frequent in FL, whereas cells with a lymphomyeloid signature were more abundant. An erythromyeloid-primed multipotent progenitor cluster was identified, potentially representing a transient, fetal-specific population. Furthermore, differentially expressed genes between fetal and adult counterparts were specifically analyzed, and a fetal core signature was identified. The core gene set could separate subgroups of acute lymphoblastic leukemia by age, suggesting that a fetal program may be partially retained in specific subgroups of pediatric leukemia. Our detailed single-cell map presented herein emphasizes molecular and immunophenotypic differences between fetal and adult blood cells, which are of significance for future studies of pediatric leukemia and blood development in general.
| S-EPMC10506049 | biostudies-literature
Project description:Hematopoiesis in Murine Fancd2-/- vs WT Fetal Liver
| PRJNA727546 | ENA
Project description:It is not clear whether disrupted age-specific hematopoiesis contributes to the complex manifestations in leukemia patients who carry identical mutations, particularly in pediatric and adult patients with similar clinical characteristics. By studying a dual-age-specific mouse model, we demonstrate: 1) loss of Pten during the fetal-to-adult hematopoiesis switch (HSC switch) causes sustained fetal hematopoiesis, resulting in death in juvenile leukemia; 2) myeloid-biased hematopoiesis in juvenile mice is associated with the sustained fetal properties of hematopoietic stem cells (HSCs); 3) the age specificity of juvenile myelomonocytic leukemia (JMML) depends on the dosage of Pten and Nf1; 4) single-allelic Pten deletion during the HSC switch causes constitutive activation of mitogen-activated protein kinase (MAPK) in juvenile mice with Nf1 loss of heterozygosity (LOH); and 5) Nf1 LOH causes monocytosis in juvenile mice with Pten haploinsufficiency but does not cause lethality until adulthood. Our data suggest that one copy of Pten is sufficient to maintain an intact negative feedback loop of the Akt pathway and HSC function in reconstitution, despite MAPK being constitutively activated in juvenile mice with Pten+/DNf1LOH. However, two copies of Pten are required to maintain the integrity of the MAPK pathway in juvenile mice with Nf1 haploinsufficiency. Our data indicate that previous investigations of Pten function in wild type mice may not reflect the impact of Pten loss in mice with Nf1 mutations or other genetic defects. We provide a proof-of-concept that disassociated age-specific hematopoiesis contributes to leukemogenesis and pediatric demise.
2020-06-25 | GSE137152 | GEO
Project description:Fetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behaviour in normal and malignant haematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse fetal and adult HSPCs. We defined the redox state of 4455 cysteines in fetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in fetal HSPCs. Our data identified ontogenically active redox switches in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified redox switches acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in fetal HSPCs. Our data has demonstrated that redox signalling contributes to the regulation of fundamental processes of developmental hematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukaemia. An H9 human embryonic stem cells cell line was applied to validate data from the primary cells.
2022-06-09 | PXD033115 | Pride
Project description:Single cell mRNA sequencing of de novo hematopoiesis from the fetal lung
| PRJNA809684 | ENA
Project description:BCL11B enhancer hijacking defines a subtype of lineage ambiguous stem cell leukemia [single-cell multiomics]
| PRJNA725192 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE36204: Epigenomic enhancer profiling defines a signature of colon cancer [ChIP-seq] GSE36400: All exon array expression data in normal colon and primary colon cancer lines [expression] Refer to individual Series
2012-04-15 | E-GEOD-36401 | biostudies-arrayexpress
Project description:To study the role of epigenetics and hormones on hematopoietic stem cell function, hematopoietic stem and progenitor (LSK) cells were sorted from E14.5 embryos of wild-type, DNMT3B7 hemizygous or DNMT3B7 homozygous genotype. The expression analysis was performed to provide information regarding the mechanism by which hormones regulate hematopoiesis. Hematopoietic stem and progenitor (LSK) cells from E14.5 murine embryonic fetal livers of wild-type, or DNMT3B7 transgenic genotypes were flow-sorted, and RNA isolated for expression analysis by RNA-Sequencing
2016-04-01 | E-GEOD-56170 | biostudies-arrayexpress