Evidence map›Paper›PMID 40961144›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Kupffer cells are essential for platelet-mediated thrombopoietin generation in the liver.

Danielle Karakas, June Li, Wenjing Ma, Xun Grace Wu, Christopher J Khoury, Mina Masoud, Brock Hoard, Yuning Jay Liu, Guangheng Zhu, Junmei Chen and 6 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Intrahepatic Platelets Orchestrate Microenvironmental Remodelling and Cellular Crosstalk in Liver Fibrosis.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  3. The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026
    Article
  4. Review
  5. Journal of clinical and experimental hepatology
    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

16 authors.

Danielle KarakasDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
June LiDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Wenjing MaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Xun Grace WuDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Christopher J KhouryDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Mina MasoudDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Brock HoardDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Yuning Jay LiuDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Guangheng ZhuDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON M5B 1T8, Canada.
Junmei ChenBloodworks Research Institute and University of Washington, Seattle, WA 98102.
Martha SimBloodworks Research Institute and University of Washington, Seattle, WA 98102.
Chuanbin ShenDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
José A LópezBloodworks Research Institute and University of Washington, Seattle, WA 98102.ORCID 0000-0002-2478-1767
Sonya A MacParlandDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Walter H A KahrToronto Platelet Immunobiology Group, University of Toronto, Toronto, ON M5B 1T8, Canada.ORCID 0000-0002-2832-7158
Heyu NiDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.ORCID 0000-0002-7621-2945

Funding

Canadian Blood Services (CBS) Intramural GrantCanadian Foundation for Innovation NACanadian Government | Canadian Institutes of Health Research (CIHR) CIHR Projects: MOP 97918; MOP 699 119540Canadian graduate scholarship master's (CGS-M) from the Canadian Institutes of Health Research (CIHR). NACanadian Institutes of Health Research Foundation Grant NAGraduate Fellowship Program Canadian Blood Services Centre for Innovation NAPostdoctoral Mitacs Award NAQueen Elizabeth II (QE-II) Graduate Scholarship NASt. Michael's Hospital Research Training Centre (RTC) Postdoc Scholarship NASt. Michael's Hospital Research Training Centre (RTC) Scholarship NAVanier Canada Graduate Scholarships (Vanier CGS) NA
6 · The paper itself

Abstract

Thrombopoietin (TPO), predominantly produced by the liver, is the key regulator for platelet production and the hematopoietic stem cell niche. Our earlier report demonstrated that platelet GPIbα is required for hepatocellular TPO generation, which is the major resource of TPO in the blood circulation. However, how hepatocytes physically contact circulating sinusoidal platelets across the liver endothelium for this process is unknown. Kupffer cells reside in contact with both sinusoidal blood and underlying hepatocytes, and mediate senescent platelet clearance, but their role in TPO regulation has never been explored. Here, we found Kupffer cell depletion via either clodronate liposomes or specific transgenic models abrogated circulating TPO. Kupffer cell depletion also prevented TPO level increase in GPIbα-deficient mice following wild-type (GPIbα

Indexed as

Blood PlateletsKupffer CellsLiverThrombopoietinAnimalsHepatocytesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPlatelet Glycoprotein GPIb-IX ComplexPlatelet TransfusionPlatelet Glycoprotein GPIb-IX ComplexThrombopoietinGPIbα and desialylationKupffer cellsliverplateletsthrombopoietin

Identifiers

PMID40961144
PMCPMC12478142

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.