Nicole A.J. Krentz
Stanford University
Enteroendocrine cellGeneInduced pluripotent stem cellInternal medicineEndocrinologyUnfolded protein responseGreen fluorescent proteinEmbryonic stem cellCellular differentiationCellProgenitorTranscriptomeAlleleProgenitor cellBeta cellEndodermType 2 diabetesPancreasContext (language use)SLC30A8Stem cellZinc Transporter 8Cell cycleGlucose homeostasisGeneticsDiabetes mellitusMedicineTranscription factorBiologyProinsulinCell biology
19Publications
8H-index
324Citations
Publications 15
Newest
#1Honey Modi (UBC: University of British Columbia)H-Index: 7
#2Chieh Min Jamie Chu (UBC: University of British Columbia)H-Index: 1
Last. James D. Johnson (UBC: University of British Columbia)H-Index: 57
view all 17 authors...
Heterogeneity within specific cell types is common and increasingly apparent with the advent of single cell transcriptomics. Transcriptional and functional cellular specialization has been described for insulin-secreting β cells of the endocrine pancreas, including so-called extreme β cells exhibiting >2-fold higher insulin gene activity. However, it is not yet clear whether β cell heterogeneity is stable or reflects dynamic cellular states. We investigated the temporal kinetics of endogenous in...
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#1Nicole A.J. Krentz (Stanford University)H-Index: 8
#2Lonnie D. Shea (UM: University of Michigan)H-Index: 83
Last. James Shaw (Newcastle University)H-Index: 32
view all 4 authors...
Summary null null Type 1 diabetes is characterised by autoimmune-mediated destruction of pancreatic β-cell mass. With the advent of insulin therapy a century ago, type 1 diabetes changed from a progressive, fatal disease to one that requires lifelong complex self-management. Replacing the lost β-cell mass through transplantation has proven successful, but limited donor supply and need for lifelong immunosuppression restricts widespread use. In this Review, we highlight incremental advances over ...
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#1Honey ModiH-Index: 7
#2Jamie ChuH-Index: 1
Last. James D. JohnsonH-Index: 57
view all 15 authors...
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#1Claire Duff (Stanford University)
#2Rikke Rejnholdt Jensen (Stanford University)
Last. Christian Honore (Stanford University)
view all 14 authors...
Heterozygous loss of function mutations in HNF1A, encoding the transcription factor hepatocyte nuclear factor 1 alpha (HNF-1A) are the most common cause of monogenic diabetes. HNF-1Ais involved in both beta cell development and mature cell function. However, model organisms have often failed to faithfully recapitulate the human phenotypes. As such, we used a patient-derived HNF1A Pro291fsinsC iPSC model and CRISPR-Cas9 genome editing to correct the mutation and generate an isogenic control. iPSC...
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Type 2 diabetes mellitus (T2DM) is an increasingly prevalent multifactorial disease that has both genetic and environmental risk factors, resulting in impaired glucose homeostasis. Genome-wide association studies (GWAS) have identified over 400 genetic signals that are associated with altered risk of T2DM. Human physiology and epigenomic data support a central role for the pancreatic islet in the pathogenesis of T2DM. This Review focuses on the promises and challenges of moving from genetic asso...
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#1Om Prakash Dwivedi (UH: University of Helsinki)H-Index: 18
#2Mikko Lehtovirta (UH: University of Helsinki)H-Index: 22
Last. Leif Groop (UH: University of Helsinki)H-Index: 170
view all 47 authors...
A rare loss-of-function allele p.Arg138* in SLC30A8 encoding the zinc transporter 8 (ZnT8), which is enriched in Western Finland, protects against type 2 diabetes (T2D). We recruited relatives of the identified carriers and showed that protection was associated with better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion, particularly when compared with individuals matched for the genotype of a common T2D-risk allele in SLC30A8, p.Arg325. In genome-edited human ...
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#1Stephanie A. Campbell (UBC: University of British Columbia)H-Index: 2
#2Cassandra McDonald (UBC: University of British Columbia)H-Index: 5
Last. Brad G. Hoffman (UBC: University of British Columbia)H-Index: 14
view all 5 authors...
Summary Appropriate regulation of genes that coordinate pancreas progenitor proliferation and differentiation is required for pancreas development. Here, we explore the role of H3K4 methylation and the Trithorax group (TrxG) complexes in mediating gene expression during pancreas development. Disruption of TrxG complex assembly, but not catalytic activity, prevented endocrine cell differentiation in pancreas progenitor spheroids. In vivo loss of TrxG catalytic activity in PDX1+ cells increased ap...
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#1Honey Modi (UBC: University of British Columbia)H-Index: 7
#2Søs Skovsø (UBC: University of British Columbia)H-Index: 11
Last. James D. Johnson (UBC: University of British Columbia)H-Index: 57
view all 15 authors...
Heterogeneity within specific cell types is common and increasingly apparent with the advent of single-cell transcriptomics. Transcriptional and functional cellular specialization has been described for insulin-secreting beta-cells of the endocrine pancreas, including so-called extreme beta-cells exhibiting more than 2 fold higher insulin gene activity. However, it is not yet clear whether beta-cell heterogeneity is stable or reflects dynamic cellular states. We investigated the temporal kinetic...
Source
#1Nicole A.J. Krentz (UBC: University of British Columbia)H-Index: 8
#2Michelle Lee (UBC: University of British Columbia)H-Index: 4
Last. Francis C. Lynn (UBC: University of British Columbia)H-Index: 29
view all 7 authors...
Summary Human embryonic stem cells (hESCs) are a potential unlimited source of insulin-producing β cells for diabetes treatment. A greater understanding of how β cells form during embryonic development will improve current hESC differentiation protocols. All pancreatic endocrine cells, including β cells, are derived from Neurog3-expressing endocrine progenitors. This study characterizes the single-cell transcriptomes of 6,905 mouse embryonic day (E) 15.5 and 6,626 E18.5 pancreatic cells isolated...
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Close Researchers
Francis C. Lynn
H-index : 29
University of British Columbia
Cuilan Nian
H-index : 21
University of British Columbia
Mei Tang
H-index : 2
University of British Columbia
Eric E. Xu
H-index : 5
University of British Columbia
Nilou Noursadeghi
H-index : 2
University of British Columbia
Rebecca Cheung
H-index : 3
Imperial College London
Michelle Lee
H-index : 4
University of British Columbia
Mark I. McCarthy
H-index : 205
University of Oxford
Derek A. Dionne
H-index : 5
University of British Columbia
Leif Groop
H-index : 170
Lund University
Reshma Ramracheya
H-index : 29
University of Oxford
Honey Modi
H-index : 7
University of British Columbia
Mark O. Huising
H-index : 38
University of California, Davis
Søs Skovsø
H-index : 11
University of British Columbia
Mikko Lehtovirta
H-index : 22
University of Helsinki
Daniela Moralli
H-index : 17
University of Oxford
Julia Brosnan
H-index : 6
Pfizer
Vikash Chandra
H-index : 8
University of Helsinki
Rashmi B. Prasad
H-index : 19
Lund University
Ola Hansson
H-index : 31
Lund University
Maddalena Trombetta
H-index : 18
University of Verona
Guy A. Rutter
H-index : 95
Imperial College London
James D. Johnson
H-index : 57
University of British Columbia
Benjamin J. Davies
H-index : 38
University of Pittsburgh
Enzo Bonora
H-index : 89
University of Verona
L Sarelin
H-index : 7
Anna L. Gloyn
H-index : 68
Stanford University
Riccardo C. Bonadonna
H-index : 66
University of Parma
Ulrika Krus
H-index : 15
Lund University
Benoit Hastoy
H-index : 12
University of Oxford
Nicola L. Beer
H-index : 16
University of Oxford
Jesper Gromada
H-index : 41
Regeneron
Tiinamaija Tuomi
H-index : 97
University of Helsinki
Om Prakash Dwivedi
H-index : 18
University of Helsinki
Evgeniy Panzhinskiy
H-index : 12
University of British Columbia
Aris Baras
H-index : 29
Regeneron
Pauline Chabosseau
H-index : 19
Imperial College London
Emma Ahlqvist
H-index : 28
Lund University
Patrik Rorsman
H-index : 110
Churchill Hospital
Timothy J. Kieffer
H-index : 69
University of British Columbia
Jason Flannick
H-index : 41
Broad Institute
Anthony J. Payne
H-index : 10
University of Oxford
Isabella Artner
H-index : 19
Lund University
Cara E. Ellis
H-index : 4
University of British Columbia
Soren K. Thomsen
H-index : 9
University of Oxford
Sandra Kleiner
H-index : 12
Regeneron
Ioannis Spiliotis
H-index : 7
University of Oxford
Jens O. Lagerstedt
H-index : 16
Lund University
Shugo Sasaki
H-index : 3
University of British Columbia
Daniel Gomez
H-index : 2
Regeneron
Benoite Champon
H-index : 1
University of Oxford
Martijn van de Bunt
H-index : 31
Novo Nordisk
Andria Theodoulou
H-index : 1
Imperial College London
Ann-Marie Richard
H-index : 2
Pfizer
Shouhong Xuan
H-index : 2
Columbia University Medical Center
Deepak Jain
H-index : 2
Lund University
Fernando Abaitua
H-index : 3
University of Oxford
Claes B. Wolheim
H-index : 1
Lund University
Timo Otonkoski
H-index : 34
University of Helsinki
Philipp Kramer
H-index : 1
University of Oxford
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