Evidence map›Paper›PMID 39122192›Full record

ArticleJournal of thrombosis and haemostasis : JTH2024

Targeting cargo to an unconventional secretory system within megakaryocytes allows the release of transgenic proteins from platelets.

Nathan L Asquith, Isabelle C Becker, Mark T Scimone, Thais Boccia, Virginia Camacho, María N Barrachina, Shihui Guo, Daniela Freire, Kellie Machlus, Sol Schulman and 2 more

Abstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Looking Under the Hood at the Cytoskeletal Engine of Platelet Production.Arteriosclerosis, thrombosis, and vascular biology · 2025
    Review
  6. Platelets welcome a new protein disulfide isomerase family member.Journal of thrombosis and haemostasis : JTH · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Nathan L AsquithVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: https://twitter.com/NathanAsquith1.
Isabelle C BeckerVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
Mark T ScimoneCellular Imaging Core, Neurobiology, Boston Children's Hospital, Boston, Massachusetts, USA; Life Sciences, Biotechnology, University of New Hampshire, Manchester, New Hampshire, USA.
Thais BocciaHarvard Medical School, Boston, Massachusetts, USA; Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
Virginia CamachoVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
María N BarrachinaVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
Shihui GuoHarvard Medical School, Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Daniela FreireVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Kellie MachlusVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
Sol SchulmanHarvard Medical School, Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Robert FlaumenhaftHarvard Medical School, Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Joseph E ItalianoVascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: Joseph.Italiano@childrens.harvard.edu.

Funding

PROGRAM IN BLOOD COAGULATION AND VASCULAR BIOLOGYT32HL007917 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Robert C Flaumenhaft · 1999 to 2026
$11.1M
Cytoskeletal Mechanisms of Platelet FormationR01HL068130 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ITALIANO, JOSEPH E · 2001 to 2021
$8.1M
Thiol Isomerases in Hemostasis and ThrombosisR35HL135775 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FLAUMENHAFT, ROBERT C · 2017 to 2023
$5.5M
The Centrosome as a master controller of platelet production.R35HL161175 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI JOSEPH E ITALIANO · 2022 to 2026
$5.3M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI FAGIOLINI, MICHELA · 2016 to 2020
$5.2M
Biomarkers and mechanisms in cancer associated thrombosisU01HL143365 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT, FLAUMENHAFT, ROBERT C · 2018 to 2022
$4.3M
The Biogenesis of Platelet-Derived Extracellular Vesicles and their Impact on Megakaryocyte MaturationR01HL151494 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI MACHLUS, KELLIE RAE · 2021 to 2025
$2.9M
Functional genetics of tissue factor in bleeding and thrombotic riskDP5OD028129 · OD · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCHULMAN, SOL · 2019 to 2023
$2.2M
Elucidation of the mechanisms by which fatty acids drive megakaryopoiesisR01DK139341 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Kellie Rae Machlus · 2024 to 2026
$1.1M
The Role of CCL5 in Hematopoietic Stem Cell Activation and SkewingR03DK124746 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MACHLUS, KELLIE RAE · 2021 to 2022
$266k
NHLBI NIH HHS R01 HL068130NHLBI NIH HHS R01 HL151494NHLBI NIH HHS R35 HL135775NHLBI NIH HHS R35 HL161175NHLBI NIH HHS T32 HL007917NHLBI NIH HHS U01 HL143365NICHD NIH HHS U54 HD090255NIDDK NIH HHS R01 DK139341NIDDK NIH HHS R03 DK124746NIH HHS DP5 OD028129
6 · The paper itself

Abstract

backgroundPlatelets are essential for hemostasis and thrombosis and play vital roles during metastatic cancer progression and infection. Hallmarks of platelet function are activation, cytoskeletal rearrangements, and the degranulation of their cellular contents upon stimulation. While α-granules and dense granules are the most studied platelet secretory granules, the dense tubular system (DTS) also functions as a secretory system for vascular thiol isomerases. However, how DTS cargo is packaged and transported from megakaryocytes (MKs) to platelets is poorly understood.

objectivesTo underpin the mechanisms responsible for DTS cargo transport and leverage those for therapeutic protein packaging into platelets.

methodsA retroviral expression system combined with immunofluorescence confocal microscopy was employed to track protein DTS cargo protein disulfide isomerase fused to enhanced green fluorescent protein (eGFP-PDI) during platelet production. Murine bone marrow transplantation models were used to determine the release of therapeutic proteins from platelets.

resultsWe demonstrated that the endoplasmic reticulum retrieval motif Lys-Asp-Glu-Leu (KDEL) located at the C-terminus of protein disulfide isomerase was essential for the regular transport of eGFP-PDI-containing granules. eGFP-PDI

conclusionOur data corroborate the DTS as a noncanonical secretory system in platelets and demonstrate that in vitro-generated MKs and platelets may be used as a delivery system for transgenic proteins during cellular therapy.

Indexed as

Blood PlateletsGreen Fluorescent ProteinsMegakaryocytesProtein Disulfide-IsomerasesAnimalsEndoplasmic ReticulumHumansMiceMice, Inbred C57BLProtein TransportSecretory VesiclesTransgenesenhanced green fluorescent proteinGreen Fluorescent ProteinsProtein Disulfide-Isomerasesgranuleshemostasismegakaryocyteplateletprotein disulfide isomerase

Identifiers

PMID39122192
PMCPMC12691161

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.