Megakaryocyte and Platelet Transcriptomics for Discoveries in Human Health and Disease

Davizon‐Castillo, Pavel; Rowley, Jesse W.; Rondina, Matthew T.

doi:10.1161/atvbaha.119.313280

Cited by 59 publications

(54 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of their relatively short lifespan, platelets are important signalling entities and could be targeted more directly during HIV-1 infection and cART, to closely evaluate and track the course of the infection. Novel approached like transcriptomics and single-cell monitoring could enable new discoveries on how platelets (and megakaryocytes) function in human health and disease (136). Although relatively low viral copies have been found in platelets (on average 9.92 HIV RNA copies per million platelets) (12); therapies targeting specifically platelets during HIV-1 infection could possibly prevent HIV-1 hiding in them.…”

Section: Discussionmentioning

confidence: 99%

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

Pretorius

2021

Front. Immunol.

View full text Add to dashboard Cite

The immune and inflammatory responses of platelets to human immunodeficiency virus 1 (HIV-1) and its envelope proteins are of great significance to both the treatment of the infection, and to the comorbidities related to systemic inflammation. Platelets can interact with the HIV-1 virus itself, or with viral membrane proteins, or with dysregulated inflammatory molecules in circulation, ensuing from HIV-1 infection. Platelets can facilitate the inhibition of HIV-1 infection via endogenously-produced inhibitors of HIV-1 replication, or the virus can temporarily hide from the immune system inside platelets, whereby platelets act as HIV-1 reservoirs. Platelets are therefore both guardians of the host defence system, and transient reservoirs of the virus. Such reservoirs may be of particular significance during combination antiretroviral therapy (cART) interruption, as it may drive viral persistence, and result in significant implications for treatment. Both HIV-1 envelope proteins and circulating inflammatory molecules can also initiate platelet complex formation with immune cells and erythrocytes. Complex formation cause platelet hypercoagulation and may lead to an increased thrombotic risk. Ultimately, HIV-1 infection can initiate platelet depletion and thrombocytopenia. Because of their relatively short lifespan, platelets are important signalling entities, and could be targeted more directly during HIV-1 infection and cART.

show abstract

Section: Discussionmentioning

confidence: 99%

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

Pretorius

2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Single-cell analyses of classically defined megakaryocyte-erythroid progenitors showed that this population contains bipotent and unipotent progenitors and that cell fate is regulated by cell cycle duration, reminiscent of myeloid-lymphoid fate choices. 16 – 19 In addition to the stepwise differentiation through megakaryocyte-erythrocyte progenitor stages, single-cell analyses have strengthened evidence that megakaryocytes can also branch directly from stem cells. 20 – 23 A third area where single-cell analyses will have high impact is the deconvolution of macrophages.…”

Section: Revision Of the Hematopoietic Hierarchymentioning

confidence: 99%

Single-Cell RNA Sequencing to Disentangle the Blood System

Acosta

Ssozi

Galen

2021

ATVB

View full text Add to dashboard Cite

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.

show abstract

“…Evidence suggests that platelets also directly influence adaptive immune processes. For example, platelets express functional CD40L (CD154) [ 17 ] and they contain a diverse spectrum of RNA species [ [18] , [19] , [20] , [21] , [22] ] packaged into platelet microvesicles (PMV) which are abundant in blood and transfused blood products [ 23 , 24 ]. PMV extend the platelet’s immunomodulation capabilities and their presence is implicated in several autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

The Immune Nature of Platelets Revisited

Maouia

Rebetz

Kapur

et al. 2020

Transfusion Medicine Reviews

113

136

View full text Add to dashboard Cite

Platelets are the primary cellular mediators of hemostasis and this function firmly acquaints them with a variety of inflammatory processes. For example, platelets can act as circulating sentinels by expressing Toll-like receptors (TLR) that bind pathogens and this allows platelets to effectively kill them or present them to cells of the immune system. Furthermore, activated platelets secrete and express many pro- and anti-inflammatory molecules that attract and capture circulating leukocytes and direct them to inflamed tissues. In addition, platelets can directly influence adaptive immune responses via secretion of, for example, CD40 and CD40L molecules. Platelets are also the source of most of the microvesicles in the circulation and these miniscule elements further enhance the platelet’s ability to communicate with the immune system. More recently, it has been demonstrated that platelets and their parent cells, the MK, can also uptake, process and present both foreign and self-antigens to CD8+ T-cells conferring on them the ability to directly alter adaptive immune responses. This review will highlight several of the non-hemostatic attributes of platelets that clearly and rightfully place them as integral players in immune reactions.

show abstract

Megakaryocyte and Platelet Transcriptomics for Discoveries in Human Health and Disease

Cited by 59 publications

References 65 publications

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

Single-Cell RNA Sequencing to Disentangle the Blood System

The Immune Nature of Platelets Revisited

Contact Info

Product

Resources

About