Evidence map›Paper›PMID 42464356›Full record

ArticleMolecular neurodegeneration2026

Transplantation of human iPSC-derived microglia ameliorates neuropathology and circuit dysfunction in progranulin-deficient mice.

Hayk Davtyan, Sarah Naguib, Yuliya Voskobiynyk, Jean Paul Chadarevian, Joia K Capocchi, Jeannie L Giacchino, Ghazaleh Eskandari-Sedighi, Vivianna DeNittis, Jeremy B Ford, Ani Agababian and 19 more

Abstract read
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In one paragraph

Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors.

Hayk Davtyan *Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Sarah Naguib *Helen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Yuliya Voskobiynyk *Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, 94158, USA.
Jean Paul ChadarevianInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Joia K CapocchiInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Jeannie L GiacchinoGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, 94158, USA.
Ghazaleh Eskandari-SedighiInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Vivianna DeNittisGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, 94158, USA.
Jeremy B FordGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, 94158, USA.
Ani AgababianDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, 92697, USA.
Jasmine NguyenInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Alina L ChadarevianInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Madison S SutherlandInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Sepideh Kiani ShabestariDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, 92697, USA.
Kayla TranInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Bret HoltGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, 94158, USA.
Alissa L NanaMemory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Jiasheng ZhangDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Salvatore SpinaMemory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Man Ying WongHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Lea T GrinbergMemory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
William W SeeleyMemory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Eric HuangDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Claire D ClellandMemory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Shiaoching GongHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Li FanHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA.
Jeanne T PazGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, 94158, USA. jeanne.paz@gladstone.ucsf.edu.
Mathew Blurton-JonesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA. mblurton@uci.edu.
Li GanHelen and Robert Appel Alzheimer's Disease Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA. lig2033@med.cornell.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Frontotemporal dementia (FTD) is a major cause of early-onset neurodegeneration characterized by progressive behavioral, emotional, and cognitive decline. Progranulin haploinsufficiency, a leading genetic cause of familial FTD, disrupts lysosomal function, lipid metabolism, autophagy, and neuroimmune signaling across multiple cell types. Increasing evidence indicates that microglia are particularly sensitive to progranulin loss, exhibiting elevated complement activation that contributes to TDP-43 proteinopathy and neuronal dysfunction. Here, we investigate the biological role of restoring progranulin exclusively within microglia by transplanting human induced pluripotent stem cell-derived microglial progenitors into progranulin (Grn)-deficient mice. We find that engraftment of wild-type, but not Grn-deficient, human microglia restore brain-wide progranulin levels, normalize microglial transcriptional states, and ameliorate pathological, functional, and behavioral phenotypes associated with progranulin loss. Because human microglia are the only source of progranulin in this system, these findings demonstrate that microglial progranulin is sufficient to restore key aspects of cellular, circuit, and behavioral homeostasis in a progranulin-deficient FTD model. More broadly, this work highlights a central, microglia-intrinsic role for progranulin in maintaining brain function and provides a framework for dissecting microglia-specific mechanisms across FTD and related neurodegenerative disorders.

Identifiers

PMID42464356

What Socratic holds

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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.