Evidence map›Paper›PMID 25908839›Full record

ArticleThe EMBO journal2015

Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro.

Holger A Russ, Audrey V Parent, Jennifer J Ringler, Thomas G Hennings, Gopika G Nair, Mayya Shveygert, Tingxia Guo, Sapna Puri, Leena Haataja, Vincenzo Cirulli and 4 more

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 380 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
380citing papers in PubMed, 1 pooled it
43.1field-weighted citation impact, top 1% 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

380 citing papers in PubMed, 1 synthesis or guideline pooled it, 574 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Charting Endocrine Progenitors Across Species and Organs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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320 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Holger A RussDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Audrey V ParentDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Jennifer J RinglerDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Thomas G HenningsDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Gopika G NairDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Mayya ShveygertEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences and Department of Urology, University of California San Francisco, San Francisco, CA, USA.
Tingxia GuoDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Sapna PuriDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Leena HaatajaDivision of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Brehm Tower Ann Arbor, MI, USA.
Vincenzo CirulliDiabetes and Obesity Center of Excellence, Department of Medicine, Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Robert BlellochEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences and Department of Urology, University of California San Francisco, San Francisco, CA, USA.
Greg L SzotDiabetes Center, University of California San Francisco, San Francisco, CA, USA.
Peter ArvanDivision of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Brehm Tower Ann Arbor, MI, USA.
Matthias HebrokDiabetes Center, University of California San Francisco, San Francisco, CA, USA mhebrok@diabetes.ucsf.edu.
University of California, San Francisco · USUniversity of Michigan–Ann Arbor · USUniversity of Washington · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
DIABETES, ENDOCRINOLOGY &METABOLISM TRAINING PROGRAMT32DK007418 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARD C HSIAO · 1986 to 2026
$14.3M
Proinsulin Trafficking for Insulin BiosynthesisR01DK048280 · NIDDK · YESHIVA UNIVERSITY · PI ARVAN, PETER · 1994 to 2024
$10.5M
NIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK063720NIDDK NIH HHS P30 DK63720NIDDK NIH HHS R01 DK048280NIDDK NIH HHS R01 DK48280NIDDK NIH HHS T32 DK007418NIDDK NIH HHS T32DK007418
6 · The paper itself

Abstract

Directed differentiation of human pluripotent stem cells into functional insulin-producing beta-like cells holds great promise for cell replacement therapy for patients suffering from diabetes. This approach also offers the unique opportunity to study otherwise inaccessible aspects of human beta cell development and function in vitro. Here, we show that current pancreatic progenitor differentiation protocols promote precocious endocrine commitment, ultimately resulting in the generation of non-functional polyhormonal cells. Omission of commonly used BMP inhibitors during pancreatic specification prevents precocious endocrine formation while treatment with retinoic acid followed by combined EGF/KGF efficiently generates both PDX1(+) and subsequent PDX1(+)/NKX6.1(+) pancreatic progenitor populations, respectively. Precise temporal activation of endocrine differentiation in PDX1(+)/NKX6.1(+) progenitors produces glucose-responsive beta-like cells in vitro that exhibit key features of bona fide human beta cells, remain functional after short-term transplantation, and reduce blood glucose levels in diabetic mice. Thus, our simplified and scalable system accurately recapitulates key steps of human pancreas development and provides a fast and reproducible supply of functional human beta-like cells.

Indexed as

Cell DifferentiationAnimalsBlood GlucoseCell Culture TechniquesCells, CulturedDiabetes Mellitus, ExperimentalEmbryonic Stem CellsGlucoseHumansInsulin-Secreting CellsMiceMice, SCIDMice, TransgenicPancreasStreptozocinBlood GlucoseGlucoseStreptozocinbeta‐like cellsdiabeteshuman embryonic stem cellsinsulin‐producing cells, pancreas

Identifiers

PMID25908839
PMCPMC4516429
OpenAlexW4234853498

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.