Sharon Lab

Pancreas Development

And Diabetes

 

The islets of Langerhans are small clusters of endocrine cells scattered throughout the pancreas. They secrete the hormones that regulate glucose levels in the body, including insulin which is secreted by the islet’s ß-cells.

In type 1 diabetes, an autoimmune attack destroys the pancreatic ß-cells, and the body loses its ability to use glucose as a source of energy and to regulate its levels in the blood.

Recent advancements in regenerative biology offer new hopes for treating the disease through transplantation of islets derived from in-vitro differentiated human embryonic stem cells.

The islets of Langerhans are small clusters of endocrine cells scattered throughout the pancreas. They secrete the hormones that regulate glucose levels in the body, including insulin which is secreted by the islet’s ß-cells. In type 1 diabetes, an autoimmune attack destroys the pancreatic ß-cells, and the body loses its ability to use glucose as a source of energy and to regulate its levels in the blood. Recent advancements in regenerative biology offer new hopes for treating the disease through transplantation of islets derived from in-vitro differentiated human embryonic stem cells.

Our lab uses cellular and animal models - combined with advanced genomic tools - to obtain better understanding of the processes that lead to islet formation during embryonic development, and applies these findings to improve the differentiation of pluripotent cells into functional, transplantable islets. In addition, we use tools from the field of developmental biology to study how the immune attack that leads to type 1 diabetes gradually progresses from its onset until the complete destruction of pancreatic ß-cells.

 
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Developmental

Biology

The Origins Of Type 1 Diabetes

Regenerative

Biology

 

We study how islets form during embryonic development to improve their production from pluripotent cells, and as as a general model to study organogenesis. We are interested in finding: how are cell-fate choices made during differentiation? How do organs acquire their shape? How do neighboring tissues interact with each other during development?

3D imaging of cleared (transparent) embryonic pancreata uncovers the layered structure of the budding peninsula.
 

We aim to identify the initial processes that trigger the immune attack which eventually leads to ß-cell destruction and to diabetes. Our efforts focus on obtaining thorough understanding of the events that take place within the “battlefield” that surrounds the islets.

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A map of the cell types which comprise the “battlefield” around the pre-diabetic islets is described using single cell RNA sequencing of NOD (non-obese diabetic) mice.
 

We look for ways to restore insulin production in diabetic patients by studying the mechanisms that allow ß-cells to proliferate, and by promoting the differentiation of human embryonic stem cells into islets, as a source for transplantation into patients.

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A cross section through a mouse pancreas shows the typical structure of the islets of Langerhans, with a core of beta cells (green) surrounded by a mantle of alpha cells (red).

Publications

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Temporal modelling using single-cell transcriptomics

Ding J, Sharon N, Bar-Joseph Z.
Nat Rev Genet. 2022 Jan 31 https://doi.org/10.1038/s41576-021-00444-7.

Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development

Sharon N, Vanderhooft J, Straubhaar J, Mueller J, Chawla R, Zhou Q, Engquist EN, Trapnell C, Gifford DK, Melton DA.
Cell Rep. 2019 May 21;27(8):2281-2291.e5.

A Peninsular Structure Coordinates Asynchronous Differentiation with Morphogenesis to Generate Pancreatic Islets

Sharon N, Chawla R, Mueller J, Vanderhooft J, Whitehorn LJ, Rosenthal B, Gürtler M, Estanboulieh

RR, Shvartsman D, Gifford DK, Trapnell C, Melton D.
Cell. 2019 Feb 7;176(4):790-804.e13

Media

3D imaging of cleared (transparent) embryonic pancreata uncovers the layered structure of the budding peninsula. . Presented is a peninsula at day 13.5 of development. Blue – alpha cells, yellow – beta cells. Red – Muc1+ chord/ductal cells.
3D imaging of cleared (transparent) embryonic pancreata uncovers the layered structure of the budding peninsula. Presented is a peninsula at day 16.5 of development. Blue – alpha cells, yellow – beta cells. Red – Muc1+ chord/ductal cells.
Time-lapse imaging of a cluster of differentiating human embryonic stem cells follows the formation of endocrine buds on the organoid’s surface
A model of islet morphogenesis.
 

Our Team

Nadav Sharon

Principal Investigator

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Esti Carmel

M.Sc. student

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Anna Parnis

Lab manager

Roy Gurwicz

M.Sc. student

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Tsofiya Szanton

M.Sc. student

Nimrod Rotem

B.Sc. student

 

We are always looking for curious, bright scientists interested in joining our team.