Evidence map›Paper›PMID 40971295›Full record

ArticleCell reports2025

Differentiation latency and dormancy signatures define fetal liver hematopoietic stem cells at single-cell resolution.

Takashi Ishida, Juliane Mercoli, Adam M Heck, Ian Phelps, Barbara Varnum-Finney, Stacey Dozono, Cynthia Nourigat-McKay, Katie Kraskouskas, Rachel Wellington, Olivia Waltner and 9 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Takashi IshidaTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Juliane MercoliTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Adam M HeckTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Ian PhelpsDepartment of Pediatrics, University of Washington, Seattle, WA, USA.
Barbara Varnum-FinneyTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Stacey DozonoTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Cynthia Nourigat-McKayTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Katie KraskouskasTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Rachel WellingtonTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Olivia WaltnerTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Dana L JacksonDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Colleen DelaneyDepartment of Pediatrics, University of Washington, Seattle, WA, USA; Seattle Children's Research Institute, Seattle, WA, USA.
Shahin RafiiDivision of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Irwin D BernsteinTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Kimberly A AldingerDepartment of Pediatrics, University of Washington, Seattle, WA, USA; Seattle Children's Research Institute, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA.
Birth Defects Research Laboratory (BDRL),Department of Pediatrics, University of Washington, Seattle, WA, USA.
Cole TrapnellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Helong G ZhaoTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: hzhao2@fredhutch.org.
Brandon HadlandTranslational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Seattle Children's Research Institute, Seattle, WA, USA. Electronic address: bhadland@fredhutch.org.

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
LABORATORY OF DEVELOPMENTAL BIOLOGYR24HD000836 · NICHD · UNIVERSITY OF WASHINGTON · PI Ian Amos Glass · 1995 to 2026
$16.9M
Hematology Central Coordinating Center (HCCC) for the NIDDK Hematology Centers ProgramU24DK126127 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Anna E Beaudin, DEREK L STIREWALT · 2020 to 2026
$7.5M
Niche signals in HSC genesisRC2DK114777 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D, RAFII, SHAHIN · 2017 to 2021
$3.3M
Dormancy-dependent determination of hematopoietic stem cell fate from hemogenic endotheliumR01HL168110 · NHLBI · FRED HUTCHINSON CANCER CENTER · PI Brandon K Hadland · 2023 to 2026
$1.8M
Probing human HSC genesis in a flow-directed 3D hemogenic vascular niche modelR01HL179317 · NHLBI · FRED HUTCHINSON CANCER CENTER · PI Brandon K Hadland, Ying Zheng · 2025 to 2026
$1.5M
Functional and transcriptional analysis of embryonic hematopoietic stem cell development at the single cell levelK08HL140143 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HADLAND, BRANDON K · 2018 to 2021
$584k
NCI NIH HHS P30 CA015704NHLBI NIH HHS K08 HL140143NHLBI NIH HHS R01 HL168110NHLBI NIH HHS R01 HL179317NICHD NIH HHS R24 HD000836NIDDK NIH HHS RC2 DK114777NIDDK NIH HHS U24 DK126127
6 · The paper itself

Abstract

Decoding the mechanisms governing the self-renewal of hematopoietic stem cells (HSCs) during their expansion in the fetal liver (FL) could unlock novel therapeutic strategies to expand transplantable HSCs, a long-standing challenge. To explore intrinsic and extrinsic regulation of FL-HSC self-renewal at single-cell resolution, we engineered a culture platform replicating the FL endothelial niche that supports the amplification of serially engraftable HSCs. Leveraging this platform together with single-cell index flow cytometry, live imaging, transplantation assays, and single-cell RNA sequencing, we demonstrate that differentiation latency, cell-division symmetry, and transcriptional signatures of biosynthetic dormancy are distinguishing properties of rare FL-HSCs capable of serial multilineage hematopoietic reconstitution. Our findings support a paradigm in which intrinsic programs and niche-derived signals together facilitate the symmetric self-renewal of FL-HSCs while delaying their active participation in hematopoiesis. Our study also provides a resource for future investigations into intrinsic and extrinsic signaling pathways governing FL-HSC self-renewal.

Indexed as

Cell DifferentiationFetusHematopoietic Stem CellsLiverSingle-Cell AnalysisAnimalsHematopoiesisMiceMice, Inbred C57BLStem Cell Nichecell division symmetryCP: Developmental biologyCP: Stem cell researchdevelopmental hematopoiesisfetal liverFLhematopoietic stem cellHSCmicroenvironmentnicheself-renewalsingle-cell RNA sequencing

Identifiers

PMID40971295
PMCPMC12587490

What Socratic 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 Socratic graph.