Unraveling Hematopoiesis through the Lens of Genomics

Liggett, L. Alexander; Sankaran, Vijay G.

doi:10.1016/j.cell.2020.08.030

Cited by 109 publications

(110 citation statements)

References 221 publications

(256 reference statements)

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“…The hematopoietic system is classically divided into two major branches during the early stage of hematopoiesis: the myeloid lineage and lymphoid lineage; one prominent function of the myeloid lineage is to establish innate immunity [ 4 , 8 , 39 ]. Myeloid lineage cells in the circulation mainly include various innate immune cells, such as monocytes, neutrophils, eosinophils, basophils, and dendritic cells (DCs).…”

Section: Relationship Between Inflammasomes and Hematopoiesismentioning

confidence: 99%

“…These cells provide general defense against external pathogens and facilitate adaptive immune responses when they encounter various stimuli. Among lymphoid lineage cells, B cells and T cells participate in adaptive immunity [ 39 , 40 ]. Rapid adaptation of the hematopoietic stem/progenitor cell (HSPC) response to severe bacterial infection leads to peripheral blood (PB) neutrophilia and is defined as emergency granulopoiesis [ 20 , 23 ].…”

Section: Relationship Between Inflammasomes and Hematopoiesismentioning

confidence: 99%

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Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Yang

et al. 2021

Molecules

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Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

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Section: Relationship Between Inflammasomes and Hematopoiesismentioning

confidence: 99%

Section: Relationship Between Inflammasomes and Hematopoiesismentioning

confidence: 99%

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Yang

et al. 2021

Molecules

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“…Although the reduction of all these processes to a few dimensions results in a continuous trajectory, not all individual regulatory mechanisms are marked by gradual change. 9 , 10 For example, some cell states can be resolved by a molecular switch, like Irf8 and Gfi1 that compete in a bipotential state to direct myeloid fate decisions. 11 Other consequential decision points are irreversible, such as enucleation during erythroid differentiation or DNA recombination during B- and T-cell differentiation.…”

Section: Revision Of the Hematopoietic Hierarchymentioning

confidence: 99%

Single-Cell RNA Sequencing to Disentangle the Blood System

Acosta

Ssozi

Galen

2021

ATVB

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The blood system is often represented as a tree-like structure with stem cells that give rise to mature blood cell types through a series of demarcated steps. Although this representation has served as a model of hierarchical tissue organization for decades, single-cell technologies are shedding new light on the abundance of cell type intermediates and the molecular mechanisms that ensure balanced replenishment of differentiated cells. In this Brief Review, we exemplify new insights into blood cell differentiation generated by single-cell RNA sequencing, summarize considerations for the application of this technology, and highlight innovations that are leading the way to understand hematopoiesis at the resolution of single cells.

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“…Hematological traits are highly heritable [1], and recent large GWAS for hematological traits (including nearly 750,000 participants) identified thousands of variant-trait associations [2,3]. With extensive sequencing and GWAS efforts, there is a need to convert large lists of significant variant-trait pairs into humaninterpretable knowledge [4]. Most variants identified through GWAS are noncoding (>95% for blood cell traits [2]), and most signals include multiple highly correlated variants.…”

Section: Introductionmentioning

confidence: 99%

“…We thus conclude that such enrichment is significant and robust to the extension of CREs. We performed analysis for three variant annotation pools (category 1, red blood cell (RBC) trait associated; category 1, any blood cell trait associated; any annotation priority category(1)(2)(3)(4)(5), any blood cell trait associated) and three CRE lengths. Fisher's exact test was applied to test for enrichment.…”

mentioning

confidence: 99%

From GWAS Variant to Function: a Study of ~148,000 Variants for Blood Cell Traits

Sun

Crowley

Huang

et al. 2021

Preprint

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Thousands of genetic loci have been identified as associated with hematological indices (red blood cell, white blood cell, and platelet related traits), as well as other complex traits and disease. However, most loci identified are noncoding and not clearly linked to target genes, and tools are needed to prioritize the most likely functional variants for experimental follow-up. We here describe VAMPIRE: Variant Annotation Method Pointing to Interesting Regulatory Effects, an interactive web application implemented in R Shiny ( http://shiny.bios.unc.edu/vampire/ ) for blood cell trait associated loci from recent large multi-ethnic genome-wide association studies (GWAS). This tool efficiently displays information from blood cell relevant tissues on epigenomic signatures, functional and conservation summary scores, variant impact on protein and gene expression, chromatin conformation information from Hi-C and similar technologies, as well as publicly available GWAS and phenome-wide association study (PheWAS) results. Variants are classified into multiple prioritization categories according to these functional signatures. Leveraging data generated from independent functional validation experiments, we demonstrate that our prioritized variants are enriched within experimentally validated variant sets. VAMPIRE allows rapid prioritization and interpretation of blood cell trait GWAS variants and could be easily adapted for use with other complex trait GWAS results and extended to new annotation sources.

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Unraveling Hematopoiesis through the Lens of Genomics

Cited by 109 publications

References 221 publications

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Single-Cell RNA Sequencing to Disentangle the Blood System

From GWAS Variant to Function: a Study of ~148,000 Variants for Blood Cell Traits

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