PXD045366-1

PXD045366 is an original dataset announced via ProteomeXchange.

Title	Insulin deficiency distorts human pancreatic endocrine cell composition during development
Description	Objective: The developmental effects of mutations in genes associated with monogenic diabetes on human pancreas development is not well understood. More specifically, if insulin gene recessive mutations influence the human endocrine lineage segregation still needs to be investigated. Methods: We generated a novel knock-in H2B-Cherry reporter human induced pluripotent stem cell (iPSCs) line expressing no insulin upon differentiation to stem cell-derived (SC-) β cells in vitro. This cell line enabled us to have a model mimicking the extremely reduced insulin levels in patients with recessive insulin mutations. We combined immunostaining, Western blotting and proteomics analysis to characterize the SC-islets from this iPSC line. Furthermore, we leveraged FACS analysis and imaging to explore the impact of insulin shortage on human endocrine cell induction, composition and proliferation. Results: We found that lack of insulin hampers insulin receptor (IR) signaling in SC-islets but increases the IR sensitivity. Furthermore, insulin deficiency showed no effects on human endocrine lineage induction. However, lack of insulin skewed the SC-islet cell composition. We found an increased in SC-β cell number at the expense of SC-α cell differentiation in the absence of insulin. Finally, insulin shortage reduced the rate of SC-β cell proliferation but had no impact of the expansion of SC-α cells. Conclusions: We provided evidence of the developmental impacts of reduced insulin levels on human β cell characteristics and endocrine lineage formation. These findings help to better understand the pathomechanisms of recessive insulin mutations during embryonic development and also shed some lights on the possible physiological function of this hormone coordinating human islet cell composition and architecture during endocrinogenesis.
HostingRepository	PRIDE
AnnounceDate	2024-01-17
AnnouncementXML	Submission_2024-01-17_06:42:12.460.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalie Krahmer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-13 15:19:46	ID requested
⏵ 1	2024-01-17 06:42:12	announced
2	2024-10-22 06:22:48	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: β cell, DIA, monogenic diabetes, islet composition,Insulin, iPSC differentiation, endocrinogenesis, LC-MS/MS

Natalie Krahmer
contact affiliation	Institute of Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany
contact email	natalie.krahmer@helmholtz-muenchen.de
lab head
Natalie Krahmer
contact affiliation	Helmholtz Center Munich
contact email	natalie.krahmer@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045366
     1. Label: PRIDE project
     2. Name: Insulin deficiency distorts human pancreatic endocrine cell composition during development