Evidence map›Paper›PMID 31523028›Full record

ArticleCell stem cell2019

Mitigating Antagonism between Transcription and Proliferation Allows Near-Deterministic Cellular Reprogramming.

Kimberley N Babos, Kate E Galloway, Kassandra Kisler, Madison Zitting, Yichen Li, Yingxiao Shi, Brooke Quintino, Robert H Chow, Berislav V Zlokovic, Justin K Ichida

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Monocyte Invasion into the Retina Restricts the Regeneration of Neurons from Müller Glia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Kimberley N BabosEli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Kate E GallowayEli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. Electronic address: katiegal@mit.edu.
Kassandra KislerZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Madison ZittingZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Yichen LiEli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
Yingxiao ShiEli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
Brooke QuintinoEli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
Robert H ChowZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Berislav V ZlokovicZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Justin K IchidaEli and Edythe Broad CIRM Center, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. Electronic address: ichida@usc.edu.

Funding

Validating Secretory Autophagy as a Therapeutic Strategy for Diverse Forms of ALS and FTDR01NS097850 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2016 to 2024
$5.5M
The role of pericytes in white matter diseaseR01NS100459 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 2016 to 2020
$3.6M
Activated protein C system in stroke modelsR01NS090904 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZLOKOVIC, BERISLAV V · 2014 to 2018
$3.2M
Lineage reprogramming for hearing loss: development of drug screening and gene therapy approachesR01DC015530 · NIDCD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA, MCMAHON, ANDREW P. · 2016 to 2020
$3.0M
KOR Agonist Functional Selectivity in Peripheral Sensory NeuronsR01DA038645 · NIDA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BERG, KELLY ANN, CLARKE, WILLIAM P · 2015 to 2019
$2.8M
Conversion of Fibroblasts to fxnal Spinal Motor Neurons Using Defined FactorR00NS077435 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2013 to 2015
$737k
Identifying the mechanisms of neuronal fate commitment during direct conversionF32NS092417 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GALLOWAY, KATE ELIZABETH · 2015 to 2017
$173k
NIDA NIH HHS R01 DA038645NIDCD NIH HHS R01 DC015530NINDS NIH HHS F32 NS092417NINDS NIH HHS R00 NS077435NINDS NIH HHS R01 NS090904NINDS NIH HHS R01 NS097850NINDS NIH HHS R01 NS100459
6 · The paper itself

Abstract

Although cellular reprogramming enables the generation of new cell types for disease modeling and regenerative therapies, reprogramming remains a rare cellular event. By examining reprogramming of fibroblasts into motor neurons and multiple other somatic lineages, we find that epigenetic barriers to conversion can be overcome by endowing cells with the ability to mitigate an inherent antagonism between transcription and DNA replication. We show that transcription factor overexpression induces unusually high rates of transcription and that sustaining hypertranscription and transgene expression in hyperproliferative cells early in reprogramming is critical for successful lineage conversion. However, hypertranscription impedes DNA replication and cell proliferation, processes that facilitate reprogramming. We identify a chemical and genetic cocktail that dramatically increases the number of cells capable of simultaneous hypertranscription and hyperproliferation by activating topoisomerases. Further, we show that hypertranscribing, hyperproliferating cells reprogram at 100-fold higher, near-deterministic rates. Therefore, relaxing biophysical constraints overcomes molecular barriers to cellular reprogramming.

Indexed as

AnimalsCell ProliferationCellular ReprogrammingDNA TopoisomerasesEpigenesis, GeneticFibroblastsGene Expression RegulationHEK293 CellsHumansInduced Pluripotent Stem CellsMiceMice, Inbred C57BLMice, TransgenicModels, BiologicalMotor NeuronsTranscription, GeneticDNA Topoisomerasesgenomic instabilityhypertranscriptionp53reprogrammingRepsoxsingle-cell RNA-seqtopoisomerasetranscription factortranscription rate

Identifiers

PMID31523028
PMCPMC6778044

What OpenQuestion holds

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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.