Evidence map›Paper›PMID 26207953›Full record

ArticleThe Journal of clinical endocrinology and metabolism2015

MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC.

Cristina Aguayo-Mazzucato, Amanda DiIenno, Jennifer Hollister-Lock, Christopher Cahill, Arun Sharma, Gordon Weir, Clark Colton, Susan Bonner-Weir

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Effects of Neurogenin 3 Induction on Endocrine Differentiation and Delamination in Adult Human Pancreatic Ductal Organoids.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
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

8 authors at 3 institutions in 1 country.

Cristina Aguayo-MazzucatoJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Amanda DiIennoJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Jennifer Hollister-LockJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Christopher CahillJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Arun SharmaJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Gordon WeirJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Clark ColtonJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Susan Bonner-WeirJoslin Diabetes Center (C.A.-M., J.H.-L., C.Ca., A.S., G.W., S.B.-W.), Harvard Medical School, Boston, Massachusetts 02215; and Department of Chemical Engineering (A.D., C.Co.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
Harvard University · USMassachusetts Institute of Technology · USJoslin Diabetes Center · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Physiological Factors Driving Maturation of Neonatal Beta CellsR01DK093909 · NIDDK · JOSLIN DIABETES CENTER · PI BONNER-WEIR, SUSAN · 2011 to 2015
$1.8M
NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK093909
6 · The paper itself

Abstract

contextHuman embryonic stem cells (hESCs) differentiated toward β-cells and fetal human pancreatic islet cells resemble each other transcriptionally and are characterized by immaturity with a lack of glucose responsiveness, low levels of insulin content, and impaired proinsulin-to-insulin processing. However, their response to stimuli that promote functionality have not been compared.

objectiveThe objective of the study was to evaluate the effects of our previous strategies for functional maturation developed in rodents in these two human models of β-cell immaturity and compare their responses. Design, Settings, Participants, and Interventions: In proof-of-principle experiments using either adenoviral-mediated overexpression of V-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) or the physiologically driven path via thyroid hormone (T3) and human fetal islet-like cluster (ICC) functional maturity was evaluated. Then the effects of T3 were evaluated upon the functional maturation of hESCs differentiated toward β-cells.

main outcome measuresFunctional maturation was evaluated by the following parameters: glucose responsiveness, insulin content, expression of the mature β-cell transcription factor MAFA, and proinsulin-to-insulin processing.

resultsICCs responded positively to MAFA overexpression and T3 treatment as assessed by two different maturation parameters: increased insulin secretion at 16.8 mM glucose and increased proinsulin-to-insulin processing. In hESCs differentiated toward β-cells, T3 enhanced MAFA expression, increased insulin content (probably mediated by the increased MAFA), and increased insulin secretion at 16.8 mM glucose.

conclusionT3 is a useful in vitro stimulus to promote human β-cell maturation as shown in both human fetal ICCs and differentiated hESCs. The degree of maturation induced varied in the two models, possibly due to the different developmental status at the beginning of the study.

Indexed as

Cell DifferentiationEmbryonic Stem CellsGlucoseHumansInsulinInsulin-Secreting CellsIslets of LangerhansMaf Transcription Factors, LargeTriiodothyronineGlucoseInsulinMAFA protein, humanMaf Transcription Factors, LargeTriiodothyronine

Identifiers

PMID26207953
PMCPMC4596039
OpenAlexW2121751945

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.