Screen for candidate ALS therapeutics (Yang, 23602540)

Astroglia regulate neuronal development (Tang, 23759711)

Modeling of late-onset disease via induced aging (Miller, 24315443)

Spinal cord astrocytes (Roybon, 23994478)

Cardiomyocyte maturation (Nunes, 23793239)

Drug screening for disease-specific cardiomyo-cyte toxicity (Liang, 23519760)

Cerebral organoids model brain development and microcephaly (Lancaster, 23995685)

Pre-rosette neural stem cell culture system (Ebert, 23474892)

Drug screening and gene correction for liver disease (Choi, 23325555)

Small molecule expansion and differentiation of hepatocytes (Shan, 23728495)

Vascular endothelium (Adams, 24052946)

Endothelium with limited variation (White, 23079999)

Vascularized, functional liver from organ bud (Takebe, 23823721)

Modeling and rescue of Williams-Beuren syndrome (Kinnear, 23283491)

cGMP expansion method for neural stem cells (Shelley, 24962813)

Hyperexcitability of ALS motor neurons (Wainger, 24703839)

Automated analysis of engi-neered heart tissue (Stoehr, 24585781)

Defined chemical conditions for cardiomyocyte generation (Burridge, 24930130)

Disease modeling and drug screening for diabetic cardiomyopathy (Drawnel, 25437537)

Heart-on-chip disease modeling of Barth syndrome cardiomyopathy (Wang, 24813252)

Epicardium (Witty, 25240927)

Retinal pigment epithelium cell sheets for clinical application (Kamao, 24527394)

Self-organizing kidney (Takasato, 24335651)

3D retina with photoreceptors (Zhong, 24915161)

Gastric organoids (McCraken, 25363776)

3D kidney via redefined nephron progenitors (Taguchi, 24332837)

Lung and airway epithelium (Huang, 24291815)

Functional β cells (Pagliuca, 25303535)

Prediction of interindividual hepatocyte drug sensitivity (Takayama, 25385620)

Cord-blood endothelium (Pra-sain, 25306246)

Hutchinson-Gilford Progeria syndrome drug responses (Blondel, 24598781)

Lithium responses in bipolar disorder neurons (Mertens, 26524527)

Atrial cardiomyocyte pharmacology assesment (Devalla, 25700171)

Contractile defect from MYBPC3 mutation (Birket, 26489474)

Cardiomyocyte contractility depends on shape and substrate stiffness (Ribeiro, 26417073)

Expansion and patterning of cardiovascular progenitors (Birket, 26192318)

Hepatocyte and cardio-toxicity high content screening (Grimm, 26539751)

Cardiac drug screening system (Mathur, 25748532)

Single contracting cardiomyocytes (Feaster, 26429802)

Bioprinted 3D mini-livers (Faulkner-Jones, 26486521)

Cholangiocytes for disease modeling and drug validation (Sampaziotis, 26167629)

Cholangiocytes (Ogawa, 26167630)

3D cortical neurons and astrocytes (Paşca, 26005811)

Predicting neural toxicity (Scwartz, 26392547)

Lung organoids (Dye, 25803487)

Multi-lineage kidney organoids for modeling nephrogenesis (Takasato, 26444236)

CRISPR-mutant kidney organoids for disease modeling (Freedman, 26493500)

Nephron organoids model kidney development and injury (Moriazane, 26458176)

Cell-cell interactions enhance hepatocyte maturation (Berger, 25421237)

Influenza in IRF7 deficiency (Ciancanelli, 25814066)

Endothelial instruction of pancreas fate (Kao, 25601205)

Engineered pulmonary vascular in decellularized lungs (Ren, 26368048)

Hemogenic and arterial endothelium have distinct origins (Ditadi, 25915127)

NOTCH1 haploinsufficiency modeling (Theodoris, 25768904)

Vascularized organ bud via mesenchymal cell condensation (Takebe, 25891906)

Modeling Duchenne muscular dystrophy in muscle fibers (Chal, 26237517)

2008

NeuronalCardiacOrganoids

EndodermMesoderm: vasculature | endothelium | muscle

2009 2010

2011

2012

Amyotrophic Lateral Sclerosis (ALS) iPSCs (Dimos, 18669821)

Parkinson’s disease iPSCs (Soldner, 19269371)

Spinal muscular atrophy iPSCs (Ebert, 19098894)

Schizophrenia (Bren-nand, 21490598)

Treatment of rat model of Parkinson’s disease (Rhee, 21576821)

Transplantable astrog-lia (Krencik, 21602806 )

Optimizing cardiomyo-cyte differentiation (Kattman, 21295278)

Cardiomyocyte sur-face markers (Elliot, 22020065; Dubois, 22020386; Uosaki, 21876760)

Self-organizing 3D optic cup (Eiraku, 21475194)

Anterior foregut endo-derm (Green, 21358635)

Treatment of a rat model of arterial disease (Rufaihah, 21836062)

20132014

2015

Drug screening for ALS (Egawa, 22855461)

Probing sporadic and familial Alzheimer’s disease (Israel, 22278060)

Modeling cardiac sodium channel disease (Davis, 22647976)

Cardiovascular progenitors (Moretti, 19850773; Blin, 20335662)

Functional cardiomy-ocytes (Zhang, 19213953)

Intestinal tissue (Spence, 21151107)

Functional hepatic endoderm (Sullivan, 19877180)

Modeling liver metabolic disorder (Rashid, 20739751)

Blood-brain barrier endothelium (Lippmann, 22729031)

Vascular smooth muscle disease susceptibility (Cheung, 22252507)

Vascular and hema-topoietic cells (Leng-erke, 19796250; Taura, 19423866; Choi, 19259936)

SnapShot: Key Advances in hiPSC Disease ModelingValeria Orlova,* Christine MummeryDepartment of Anatomy and Embryology, Leiden University Medical Centre, Einthovenweg 20, 2333ZC Leiden, The Netherlands

This SnapShot presents a timeline of key advances in directed differentiation

and disease modeling using human pluripotent stem cells. The PMID for

each paper is listed after the first author’s name, and the papers are grouped

by color codes referring to different systems. A related Review by Passier et

al. (2016) in this issue of Cell Stem Cell provides further analysis of key

advances in hiPSCs over the last 10 years.

Bio-Techne™ provides an outstanding selection of high-quality reagents and assays for studying lipid metabolism, glucose homeostasis, and energy balance. For more information on innovative tools for Life Science Research, Therapeutic Manufacturing, and Clinical Diagnostics, please visit us at bio-techne.com.

Join Cell Press and Bio-Techne in celebrating the 100th anniversary of the discovery of insulin. To access a virtual panel discussion, downloadable research collections, and a PDF of this poster, visit cell.com/insulin.

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An Egyptian papyrus describes symptoms compatible with diabetes

CB0551 Banting and Best extract insulin

injected to treat another dog with diabetes

Banting and Macleodare awarded the Nobel Prize for the discovery of insulin

32913291

Leonard Thompson is the first patient with diabetes treated with insulin at a Toronto hospital

2291

Timeline: 0191

Insulin deficiencyis identified as the cause of diabetes

Insulin becomes commercially availableEli Lilly startslarge-scaleproduction of insulin from cattle and pigs

Release of an extended action insulin by Novo Nordisk

6391

Release ofSulfonylureas

5591 Oral medication that stimulates insulin secretionfrom pancreas

8591

Frederick Sangeris awarded theNobel Prize for the structure of insulinInsulin becomes thefirst protein to be sequenced

9591

Classification of diabetes as “type 1” or “insulin dependent” and “type 2” or “insulinindependent”

Metformin is introduced as an antihyperglycemicagent

9591

First successful pancreas transplantationat University of MinnesotaHealth

6691

Produced by the pancreas, glucagon raises blood glucose

1691

Glucagonbecomes commercially available to treathypoglycemia

8791

Geneticallyengineeredhuman insulinGenentech clones the human insulin gene

The first synthetic human insulin is commercialized as Humulin

2891s09- s0891

Insulin pen,insulin pump,continuous glucosemonitoring

Developmentof devices to manage diabetes

0002

5002

Publication of the “Edmonton Protocol”to treat T1D withtransplanted islets

s0202

Immunotherapy for

areas of research

Future possibilities

CellMetabolism

First records of diabetes cases 3102

First SGLT2 inhibitor isapproved formedical useOral medication thatreduces glucose reabsorption from blood in thekidneys

Insulin and diabetes

1291

Centennialof insulindiscovery

1202

1925 1950 1975 2000

extracts, making clinical applicationpossible

GLP-1agonist isapproved for medicaluse

Partially restores insulin production

term glycemic control and Science, NMAH, Smithsonian Institution