Evidence map›Paper›PMID 35971894›Full record

ArticleEMBO reports2022

Identification and characterization of in vitro expanded hematopoietic stem cells.

James L C Che, Daniel Bode, Iwo Kucinski, Alyssa H Cull, Fiona Bain, Hans J Becker, Maria Jassinskaja, Melania Barile, Grace Boyd, Miriam Belmonte and 11 more

Abstract read
In one paragraph

Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

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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

21 authors.

James L C Che *Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0003-4621-8649
Daniel Bode *Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Iwo KucinskiWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0002-9385-0359
Alyssa H CullDepartment of Biology, York Biomedical Research Institute, University of York, York, UK.
Fiona BainDepartment of Biology, York Biomedical Research Institute, University of York, York, UK.ORCID 0000-0002-2278-1851
Hans J BeckerDivision of Stem Cell Biology, Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Maria JassinskajaDepartment of Biology, York Biomedical Research Institute, University of York, York, UK.
Melania BarileWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Grace BoydDepartment of Biology, York Biomedical Research Institute, University of York, York, UK.ORCID 0000-0003-1037-9045
Miriam BelmonteWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Andy G X ZengPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Kyomi J IgarashiDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-4352-3835
Juan Rubio-LaraDepartment of Biology, York Biomedical Research Institute, University of York, York, UK.
Mairi S ShepherdWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Anna ClayWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
John E DickPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-9527-8317
Adam C WilkinsonMRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Hiromitsu NakauchiDivision of Stem Cell Biology, Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Satoshi YamazakiDivision of Stem Cell Biology, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID 0000-0003-4249-3854
Berthold GöttgensWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0001-6302-5705
David G KentWellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0001-7871-8811

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council 203151/Z/16/ZMedical Research Council MC_PC_17230Medical Research Council MR/V005502/1Wellcome Trust
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200-fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non-HSCs and single cell-initiated cultures have substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures. By directly linking single-clone functional transplantation data with single-clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This "repopulation signature" (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.

Indexed as

Follistatin-Related ProteinsAnimalsCells, CulturedEndothelial Protein C ReceptorHematopoietic Stem CellsHumansMiceTranscription FactorsEndothelial Protein C ReceptorFollistatin-Related ProteinsFSTL1 protein, humanTranscription Factorshematopoiesishematopoietic stem cellsHSC expansionself-renewal gene signaturesingle cell biology

Identifiers

PMID35971894
PMCPMC9535767

What OpenQuestion 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 OpenQuestion graph.