Evidence map›Paper›PMID 27480112›Full record

ArticleBlood2016

EKLF/KLF1-regulated cell cycle exit is essential for erythroblast enucleation.

Merlin Nithya Gnanapragasam, Kathleen E McGrath, Seana Catherman, Li Xue, James Palis, James J Bieker

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

65 citing papers in PubMed, 86 citations in OpenAlex.

  1. Trial
  2. Article
  3. ReducedInternational journal of molecular sciences · 2026
    Article
  4. Orai1 acts as a novel CaExperimental & molecular medicine · 2026
    Article
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  13. Article
  14. Erythroblast enucleation at a glance.Journal of cell science · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

5 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 at 2 institutions in 1 country.

Merlin Nithya GnanapragasamDepartment of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY; and.
Kathleen E McGrathCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY.
Seana CathermanCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY.
Li XueDepartment of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY; and.
James PalisCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY.
James J BiekerDepartment of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY; and.
Icahn School of Medicine at Mount Sinai · USUniversity of Rochester Medical Center · US

Funding

Ontogeny of erythroid lineage differentiationR01DK071116 · NIDDK · UNIVERSITY OF ROCHESTER · PI PALIS, JAMES · 2006 to 2010
$2.2M
Role of EPO in terminal erythroid maturationR01HL116364 · NHLBI · UNIVERSITY OF ROCHESTER · PI PALIS, JAMES · 2012 to 2015
$1.5M
Intrinsic and extrinsic control of erythropoietic maturationR01DK102260 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BIEKER, JAMES J · 2014 to 2017
$1.5M
NHLBI NIH HHS R01 HL116364NIDDK NIH HHS R01 DK071116NIDDK NIH HHS R01 DK102260
6 · The paper itself

Abstract

The mechanisms regulating the sequential steps of terminal erythroid differentiation remain largely undefined, yet are relevant to human anemias that are characterized by ineffective red cell production. Erythroid Krüppel-like Factor (EKLF/KLF1) is a master transcriptional regulator of erythropoiesis that is mutated in a subset of these anemias. Although EKLF's function during early erythropoiesis is well studied, its role during terminal differentiation has been difficult to functionally investigate due to the impaired expression of relevant cell surface markers in Eklf(-/-) erythroid cells. We have circumvented this problem by an innovative use of imaging flow cytometry to investigate the role of EKLF in vivo and have performed functional studies using an ex vivo culture system that enriches for terminally differentiating cells. We precisely define a previously undescribed block during late terminal differentiation at the orthochromatic erythroblast stage for Eklf(-/-) cells that proceed beyond the initial stall at the progenitor stage. These cells efficiently decrease cell size, condense their nucleus, and undergo nuclear polarization; however, they display a near absence of enucleation. These late-stage Eklf(-/-) cells continue to cycle due to low-level expression of p18 and p27, a new direct target of EKLF. Surprisingly, both cell cycle and enucleation deficits are rescued by epistatic reintroduction of either of these 2 EKLF target cell cycle inhibitors. We conclude that the cell cycle as regulated by EKLF during late stages of differentiation is inherently critical for enucleation of erythroid precursors, thereby demonstrating a direct functional relationship between cell cycle exit and nuclear expulsion.

Indexed as

AnimalsBinding SitesCell Cycle CheckpointsCell DifferentiationCell NucleusCells, CulturedEmbryo, MammalianErythroblastsErythropoiesisGene Expression Regulation, DevelopmentalKruppel-Like Transcription FactorsLiverMiceMice, Inbred C57BLMice, Knockouterythroid Kruppel-like factorKruppel-Like Transcription Factors

Identifiers

PMID27480112
PMCPMC5034741
OpenAlexW2497166756

What OpenQuestion holds

Textmetadata
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.