Evidence map›Paper›PMID 24711581›Full record

ArticleThe Journal of experimental medicine2014

Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation.

Adlen Foudi, Daniel J Kramer, Jinzhong Qin, Denise Ye, Anna-Sophie Behlich, Scott Mordecai, Frederic I Preffer, Arnaud Amzallag, Sridhar Ramaswamy, Konrad Hochedlinger and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
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

37 citing papers in PubMed, 52 citations in OpenAlex.

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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

12 authors at 4 institutions in 2 countries.

Adlen FoudiCancer Center, 2 Center for Regenerative Medicine, and 3 Department of Pathology, Massachusetts General Hospital, 4 Harvard Medical School, Boston, MA 02114.
Daniel J Kramer
Jinzhong Qin
Denise Ye
Anna-Sophie Behlich
Scott Mordecai
Frederic I Preffer
Arnaud Amzallag
Sridhar Ramaswamy
Konrad Hochedlinger
Stuart H Orkin
Hanno Hock
Massachusetts General Hospital · USCenter for Neuroscience and Regenerative Medicine · USHarvard University · USHarvard Stem Cell Institute · US

Funding

MOLECULAR ANALYSIS OF NORMAL AND TYHALASSEMIC DNAR01HL032259 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1985 to 2022
$8.8M
Gfi-proteins in Hematopoietic DevelopmentR01HL075735 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI ORKIN, STUART H · 2004 to 2013
$4.2M
Function of zinc-finger transcription factor Gfi-1 in hematopoietic stem cellsR01CA122726 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HOCK, HANNO R · 2007 to 2011
$1.7M
Role of Sox2 in stomach development, regeneration and cancerR01DK096034 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2012 to 2015
$1.4M
ImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595k
Howard Hughes Medical InstituteNCI NIH HHS C06 CA599267NCI NIH HHS R01 CA122726NCI NIH HHS R01CA122726NHLBI NIH HHS R01 HL032259NHLBI NIH HHS R01 HL075735NHLBI NIH HHS R01HL075735NIDDK NIH HHS R01 DK096034NIDDK NIH HHS R01DK096034-01NIH HHS S10 OD012027NIH HHS S10OD012027PHS HHS T32 2012D006265
6 · The paper itself

Abstract

The zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b's adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow. We reveal strict, lineage-intrinsic requirements for continuous adult Gfi-1b expression at two distinct critical stages of erythropoiesis and megakaryopoiesis. Induced disruption of Gfi-1b was lethal within 3 wk with severely reduced hemoglobin levels and platelet counts. The erythroid lineage was arrested early in bipotential progenitors, which did not give rise to mature erythroid cells in vitro or in vivo. Yet Gfi-1b(-/-) progenitors had initiated the erythroid program as they expressed many lineage-restricted genes, including Klf1/Eklf and Erythropoietin receptor. In contrast, the megakaryocytic lineage developed beyond the progenitor stage in Gfi-1b's absence and was arrested at the promegakaryocyte stage, after nuclear polyploidization, but before cytoplasmic maturation. Genome-wide analyses revealed that Gfi-1b directly regulates a wide spectrum of megakaryocytic and erythroid genes, predominantly repressing their expression. Together our study establishes Gfi-1b as a master transcriptional repressor of adult erythropoiesis and thrombopoiesis.

Indexed as

AnimalsBlood PlateletsBone MarrowDNA PrimersEmbryonic Stem CellsErythrocytesFlow CytometryGene Expression RegulationGenetic VectorsHematopoiesisKaplan-Meier EstimateMiceMice, TransgenicMicroarray AnalysisMicroscopy, FluorescenceMutagenesisDNA PrimersGfi1b protein, mouseProto-Oncogene ProteinsRepressor Proteins

Identifiers

PMID24711581
PMCPMC4010908
OpenAlexW2138099034

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.