Evidence map›Paper›PMID 34471104›Full record

ArticleNature communications2021

Improved modeling of human AD with an automated culturing platform for iPSC neurons, astrocytes and microglia.

Reina Bassil, Kenneth Shields, Kevin Granger, Ivan Zein, Shirley Ng, Ben Chih

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing 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

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

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7 more citing papers are in PubMed but not listed here.

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

6 authors.

Reina BassilDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, USA.
Kenneth ShieldsDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, USA.ORCID 0000-0002-4179-2863
Kevin GrangerDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, USA.ORCID 0000-0003-0154-0693
Ivan ZeinDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, USA.
Shirley NgDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, USA.ORCID 0000-0002-9991-3891
Ben ChihDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, USA. ben.chih@gmail.com.ORCID 0000-0002-1248-8379

Funding

Pathways in Biological Sciences Training ProgramT32GM133351 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Matthew Daugherty, Randolph Y. Hampton · 2020 to 2026
$9.9M
NIGMS NIH HHS T32 GM133351
6 · The paper itself

Abstract

Advancement in human induced pluripotent stem cell (iPSC) neuron and microglial differentiation protocols allow for disease modeling using physiologically relevant cells. However, iPSC differentiation and culturing protocols have posed challenges to maintaining consistency. Here, we generated an automated, consistent, and long-term culturing platform of human iPSC neurons, astrocytes, and microglia. Using this platform we generated a iPSC AD model using human derived cells, which showed signs of Aβ plaques, dystrophic neurites around plaques, synapse loss, dendrite retraction, axon fragmentation, phospho-Tau induction, and neuronal cell death in one model. We showed that the human iPSC microglia internalized and compacted Aβ to generate and surround the plaques, thereby conferring some neuroprotection. We investigated the mechanism of action of anti-Aβ antibodies protection and found that they protected neurons from these pathologies and were most effective before pTau induction. Taken together, these results suggest that this model can facilitate target discovery and drug development efforts.

Indexed as

Alzheimer DiseaseAstrocytesCell DifferentiationHumansInduced Pluripotent Stem CellsKineticsMicrogliaNeuronsPlaque, AmyloidSynapses

Identifiers

PMID34471104
PMCPMC8410795

What OpenQuestion holds

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LicenceCC BY
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.