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Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

ABSTRACT: Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

PROVIDER: PRJNA1075299 | ENA |

REPOSITORIES: ENA

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Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

Project description:Understanding how intra-tumoral immune populations coordinate to generate anti-tumor responses following therapy can guide precise treatment prioritization. We performed systematic dissection of an established adoptive cellular therapy, donor lymphocyte infusion (DLI) by analyzing 348,905 single-cell transcriptomes from 74 longitudinal bone-marrow samples of 25 patients with relapsed myeloid leukemia; with a subset evaluated by protein-based spatial analysis. In acute myelogenous leukemia (AML) responders, diverse immune cell types within the bone-marrow microenvironment (BME) were predicted to interact with a clonally expanded population of ZNF683+GZMB+ CD8+ cytotoxic T lymphocytes (CTLs) which demonstrated in vitro specificity for autologous leukemia. This population, originating predominantly from the DLI product, expanded concurrently with NK and B cells. AML nonresponder BME revealed a paucity of crosstalk and elevated TIGIT expression in CD8+ CTLs. Our study highlights recipient BME differences as a key determinant of effective anti-leukemia response and opens new opportunities to modulate cell-based leukemia-directed therapy.

2025-01-24 | GSE255530 | GEO

Identifying Coordinated Gene Regulatory Networks That Direct Cardiomyocyte Development

Project description:Identifying Coordinated Gene Regulatory Networks That Direct Cardiomyocyte Development

| PRJNA1028604 | ENA

Identifying Coordinated Gene Regulatory Networks That Direct Cardiomyocyte Development

Project description:Illuminating the precise stepwise genetic programs directing cardiac development provides insights into the mechanisms of congenital heart disease and strategies for cardiac regenerative therapies. Here, we integrated in vitro and in vivo human single-cell multi-omic studies with high-throughput functional genomic screening to reveal dynamic, cardiac-specific gene regulatory networks and transcriptional regulators during human cardiomyocyte development. Interrogating developmental trajectories reconstructed from single-cell data unexpectedly revealed divergent cardiomyocyte lineages with distinct gene programs based on developmental signaling pathways. High-throughput functional genomic screens identified key transcription factors from inferred gene regulatory networks (GRNs) that were functionally relevant for cardiomyocyte lineages derived from each pathway. Notably, we discovered a critical HSF1-mediated cardiometabolic GRN controlling cardiac mitochondrial/metabolic function and cell survival, also observed in fetal human cardiomyocytes. Overall, these multi-modal genomic studies enabled the systematic discovery and validation of coordinated gene regulatory networks and transcriptional regulators controlling the development of distinct human cardiomyocyte populations.

2024-09-06 | GSE245499 | GEO

Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [visium]

Project description:We and others have demonstrated Zika virus (ZIKV) congenital infection evades double-stranded RNA detection, and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. We used orthogonal approaches to test the hypothesis that ZIKV disrupts placental miRNAs to enable viral persistence and fetal pathogenesis. In primary human trophoblasts, high-throughput sequencing crosslinking and immunoprecipitation (AGO-HITS-CLIP) demonstrated an unexpected disruption of placental miRNA-regulated TGF-β networks. In gnotobiotic mice, absence of microbes rendered normally resistant mice susceptible to congenital ZIKV infection, and placental spatial transcriptomics revealed distinct microenvironments defined by significant upregulation of complement cascade components. Finally, treatment of ZIKV-infected mice with the RNAi-enhancer enoxacin led to loss of ZIKV placental persistence and rescue of fetal growth restriction. These results collectively suggest that ZIKV co-opts miRNA inflammatory regulatory networks to persist in the placenta reservoir, a conduit of vertical transmission and fetal pathogenesis.

2023-06-03 | GSE205631 | GEO

Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics

Project description:Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics

| PRJNA846741 | ENA

Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [AGO-HITS-CLIP]

2023-06-03 | GSE205609 | GEO

Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [visium]

Project description:Zika virus co-opts miRNA networks to persist in placental microenvironments detected by spatial transcriptomics [visium]

| PRJNA846745 | ENA

Coordinated Cross-Talk Between the Myc and Mlx Networks in Liver Regeneration and Neoplasia

Project description:Coordinated Cross-Talk Between the Myc and Mlx Networks in Liver Regeneration and Neoplasia

| PRJNA751862 | ENA

Transcriptomes distinguish human FCD subtypes

Project description:Transcriptomes distinguish human FCD subtypes

| PRJNA527060 | ENA

microRNAs distinguish cytogenetic subgroups in pediatric AML and contribute to complex regulatory networks in AML-relevant pathways

Project description:microRNAs distinguish cytogenetic subgroups in pediatric AML and contribute to complex regulatory networks in AML-relevant pathways

| PRJNA150757 | ENA

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