Summary of Study ST004277

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002703. The data can be accessed directly via it's Project DOI: 10.21228/M88851 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST004277
Study Title	Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells
Study Summary	Pluripotent stem cell (SC)-derived islets offer hope as a renewable source for β cell replacement for type 1 diabetes (T1D), yet functional and metabolic immaturity may limit their long-term therapeutic potential. Here, we show that limitations in mitochondrial transcriptional programming impede the formation of SC-derived β (SC-β) cells. Utilizing transcriptomic profiling, assessments of chromatin accessibility, mitochondrial phenotyping, and lipidomics analyses, we observed that SC-β cells exhibit reduced oxidative and mitochondrial fatty acid metabolism compared to primary human islets that are related to limitations in key mitochondrial transcriptional networks. Surprisingly, we find that reductions in glucose-stimulated mitochondrial respiration in SC-islets were not associated with alterations in mitochondrial mass, structure, or genome integrity. In contrast, SC-islets show limited expression of targets of PPAR⍺, which regulate mitochondrial programming, yet whose functions in β cell differentiation are unknown. Importantly, treatment with WY14643, a potent PPAR⍺ agonist, induced expression of mitochondrial targets, improved insulin secretion, and increased the formation of SC-β cells both in vitro and following transplantation. Thus, PPAR⍺-dependent mitochondrial programming promotes the differentiation of SC-β cells and may be a promising target to improve β cell replacement efforts for T1D.
Institute	University of Michigan
Department	Division of Metabolism, Endocrinology and Diabetes and Department of Internal Medicine
Laboratory	Scott A. Soleimanpour
Last Name	Arnipalli
First Name	Manikanta
Address	3815-301B Green Brier apt, Ann Arbor, michigan, 48105, USA
Email	manikana@umich.edu
Phone	734-272-8779
Submit Date	2025-10-10
Raw Data Available	Yes
Raw Data File Type(s)	mzML, d
Analysis Type Detail	LC-MS
Release Date	2025-10-31
Release Version	1

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Project:

Project ID:	PR002703
Project DOI:	doi: 10.21228/M88851
Project Title:	Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells
Project Summary:	Pluripotent stem cell (SC)-derived islets offer hope as a renewable source for β cell replacement for type 1 diabetes (T1D), yet functional and metabolic immaturity may limit their long-term therapeutic potential. Here, we show that limitations in mitochondrial transcriptional programming impede the formation of SC-derived β (SC-β) cells. Utilizing transcriptomic profiling, assessments of chromatin accessibility, mitochondrial phenotyping, and lipidomics analyses, we observed that SC-β cells exhibit reduced oxidative and mitochondrial fatty acid metabolism compared to primary human islets that are related to limitations in key mitochondrial transcriptional networks. Surprisingly, we find that reductions in glucose-stimulated mitochondrial respiration in SC-islets were not associated with alterations in mitochondrial mass, structure, or genome integrity. In contrast, SC-islets show limited expression of targets of PPAR⍺, which regulate mitochondrial programming, yet whose functions in β cell differentiation are unknown. Importantly, treatment with WY14643, a potent PPAR⍺ agonist, induced expression of mitochondrial targets, improved insulin secretion, and increased the formation of SC-β cells both in vitro and following transplantation. Thus, PPAR⍺-dependent mitochondrial programming promotes the differentiation of SC-β cells and may be a promising target to improve β cell replacement efforts for T1D.
Institute:	University of Michigan
Department:	Division of Metabolism, Endocrinology and Diabetes and Department of Internal Medicine
Laboratory:	Scott A. Soleimanpour
Last Name:	Arnipalli
First Name:	Manikanta
Address:	3815-301B Green Brier apt, Ann Arbor, michigan, 48105, USA
Email:	manikana@umich.edu
Phone:	734-272-8779

Subject:

Subject ID:	SU004430
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	Sample type	Sample source	Glucose Concentration
SA498049	Blank_02_human	Human_Control	Pancreas	NA
SA498050	AS_A_mouse_high	Human_Control	Pancreas	NA
SA498051	AS_B_mouse_high	Human_Control	Pancreas	NA
SA498052	bank_04_mouse_high	Human_Control	Pancreas	NA
SA498053	Blank_01_mouse_high	Human_Control	Pancreas	NA
SA498054	pool_05_human	Human_Control	Pancreas	NA
SA498055	pool_04_human	Human_Control	Pancreas	NA
SA498056	pool_03_human	Human_Control	Pancreas	NA
SA498057	pool_02_human	Human_Control	Pancreas	NA
SA498058	Blank_04_human	Human_Control	Pancreas	NA
SA498059	pool_01_human	Human_Control	Pancreas	NA
SA498060	Blank_01_human	Human_Control	Pancreas	NA
SA498061	pool_02_mouse_high	Human_Control	Pancreas	NA
SA498062	pool_06_mouse_high	Human_Control	Pancreas	NA
SA498063	pool_05_mouse_high	Human_Control	Pancreas	NA
SA498064	AS_B_human	Human_Control	Pancreas	NA
SA498065	pool_03_mouse_high	Human_Control	Pancreas	NA
SA498066	pool_04_mouse_high	Human_Control	Pancreas	NA
SA498067	pool_01_mouse_high	Human_Control	Pancreas	NA
SA498068	Blank_03_mouse_high	Human_Control	Pancreas	NA
SA498069	Blank_02_mouse_high	Human_Control	Pancreas	NA
SA498070	AS_A_human	Human_Control	Pancreas	NA
SA498071	9/18/22 S3 metabolomics 20mM	Human	Pancreas	High
SA498072	10/08/22 S6 metabolomics 20mM	Human	Pancreas	High
SA498073	10/04/22 S6 metabolomics 20mM	Human	Pancreas	High
SA498074	9/29/22 S5 metabolomics 20mM	Human	Pancreas	High
SA498075	10-04-22 Human islets 20mM	Human	Pancreas	High
SA498076	9/22/22 S4 metabolomics 20mM	Human	Pancreas	High
SA498077	9/18/22 S4 metabolomics 20mM	Human	Pancreas	High
SA498078	9/25/22 S5 metabolomics 20mM	Human	Pancreas	High
SA498079	9/16/22 S2 metabolomics 20mM	Human	Pancreas	High
SA498080	9/14/22 S3 metabolomics 20mM	Human	Pancreas	High
SA498081	10-07-22 Human islets 20mM	Human	Pancreas	High
SA498082	10-15-22 Human islets 20mM	Human	Pancreas	High
SA498083	10-28-22 Alberta Human islets 20mM	Human	Pancreas	High
SA498084	10-28-22 Prodo Human islets 20mM	Human	Pancreas	High
SA498085	7/22/22 S1 metabolomics 20mM	Human	Pancreas	High
SA498086	7/24/22 S2 metabolomics 20mM	Human	Pancreas	High
SA498087	7/26/22 S3 metabolomics 20mM	Human	Pancreas	High
SA498088	7/30/22 S4 metabolomics 20mM	Human	Pancreas	High
SA498089	8/06/22 S5 metabolomics 20mM	Human	Pancreas	High
SA498090	8/15/22 S6 metabolomics 20mM	Human	Pancreas	High
SA498091	9/10/22 S1 metabolomics 20mM	Human	Pancreas	High
SA498092	9/12/22 S2 metabolomics 20mM	Human	Pancreas	High
SA498093	9/14/22 S1 metabolomics 20mM	Human	Pancreas	High
SA498094	9-16-22 S2 metabolomics 5.5mM	Human	Pancreas	Low
SA498095	9-18-22 S3 metabolomics 5.5mM	Human	Pancreas	Low
SA498096	9-18-22 S4 metabolomics 5.5mM	Human	Pancreas	Low
SA498097	9-22-22 S4 metabolomics 5.5mM	Human	Pancreas	Low
SA498098	10-08-22 S6 metabolomics 5.5mM	Human	Pancreas	Low
SA498099	9-25-22 S5 metabolomics 5.5mM	Human	Pancreas	Low
SA498100	9-29-22 S5 metabolomics 5.5mM	Human	Pancreas	Low
SA498101	10-04-22 S6 metabolomics 5.5mM	Human	Pancreas	Low
SA498102	9-14-22 S1 metabolomics 5.5mM	Human	Pancreas	Low
SA498103	9-14-22 S3 metabolomics 5.5mM	Human	Pancreas	Low
SA498104	7-22-22 S1 metabolomics 5.5mM	Human	Pancreas	Low
SA498105	9-12-22 S2 metabolomics 5.5mM	Human	Pancreas	Low
SA498106	9-10-22 S1 metabolomics 5.5mM	Human	Pancreas	Low
SA498107	8-15-22 S6 metabolomics 5.5mM	Human	Pancreas	Low
SA498108	8-06-22 S5 metabolomics 5.5mM	Human	Pancreas	Low
SA498109	7-30-22 S4 metabolomics 5.5mM	Human	Pancreas	Low
SA498110	7-26-22 S3 metabolomics 5.5mM	Human	Pancreas	Low
SA498111	7-24-22 S2 metabolomics 5.5mM	Human	Pancreas	Low
SA498112	10-07-22 Human islets 5.5mM	Human	Pancreas	Low
SA498113	10-15-22 Human islets 5.5mM	Human	Pancreas	Low
SA498114	10-28-22 Alberta Human islets 5.5mM	Human	Pancreas	Low
SA498115	10-28-22 Prodo Human islets 5.5mM	Human	Pancreas	Low
SA498116	10-04-22 Human islets 5.5mM	Human	Pancreas	Low

Showing results 1 to 68 of 68

Showing results 1 to 68 of 68

Collection:

Collection ID:	CO004423
Collection Summary:	Cells were cultured according to Hogrebe et al4. On the day of sample collection, samples were incubated in MCDB 131 with 10.5 g BSA, 5.2 mL GlutaMAX, 5.2 mL P/S, 5 mg heparin, 5.2 mL MEM nonessential amino acids (Corning, 20–025-CI), 84 μg ZnSO4 (MilliporeSigma, 10883), 523 μL Trace Elements A (Corning, 25–021-CI), and 523 μL Trace Elements B (Corning, 25–022-CI) and either 5.5mM or 20mM glucose for 3 hr. Media was removed, and the cells were washed 1X with ice-cold 150 mM ammonium acetate in LC-MS grade water. Cells were harvested with 200 μL of ice-cold methanol and frozen at -80°C until sample preparation.
Sample Type:	Pancreas

Treatment:

Treatment ID:	TR004439
Treatment Summary:	Treatment not applied.

Sample Preparation:

Sampleprep ID:	SP004436
Sampleprep Summary:	For extraction, 200 μL of cold water was added to the cells and the cells were scraped. The resulting homogenate was sonicated on ice for 10 sec. 400 μL of chloroform was added. Samples were centrifuged at 17,000 x g for 10 min and the resulting top layer was collected and taken to dryness under nitrogen. Samples were reconstituted in 30 μL of 2:1 ACN: water, filtered and 5 μL were injected for analysis.

Sampleprep ID:

SP004436

Sampleprep Summary:

For extraction, 200 μL of cold water was added to the cells and the cells were scraped. The resulting homogenate was sonicated on ice for 10 sec. 400 μL of chloroform was added. Samples were centrifuged at 17,000 x g for 10 min and the resulting top layer was collected and taken to dryness under nitrogen. Samples were reconstituted in 30 μL of 2:1 ACN: water, filtered and 5 μL were injected for analysis.

Chromatography:

Chromatography ID:	CH005406
Chromatography Summary:	Metabolites were separated on an InfinityLab Poroshell120 HILIC-Z, 2.7 μm, 2.1 × 150 mm column (Agilent Technologies, CA, USA). Mobile phase A was composed of 90% 10 mM ammonium acetate pH 9.0 with ammonia, 10% acetonitrile (ACN) with 2.5 uM InfinityLab Deactivator Additive (Agilent Technologies, CA, USA) and mobile phase B was composed of 15% 10 mM ammonium acetate pH 9.0 with ammonia, 85% acetonitrile with 2.5 uM InfinityLab Deactivator Additive. The flow rate was 0.25 mL/min, and the gradient was as follows: 0-2 min at 95 % B, 2-5 min at 95% B, 5-5.5 min at 86%, 5.5-8.5 min at 86% B, 8.5-9 min at 84% B, 9-14 min at 84% B, 14-17 min at 80% B, 17-23 min at 60% B, 23-26 min at 60% B, 26-27 min at 95% B, and 27-35 min at 95% B. Column compartment temperature was kept at 25 °C. Data were acquired in negative mode.
Instrument Name:	Agilent 1290 Infinity II
Column Name:	Agilent Poroshell120 HILIC-Z (150 x 2.1 mm, 2.7 μm)
Column Temperature:	25°C
Flow Gradient:	0-2 min at 95 % B, 2-5 min at 95% B, 5-5.5 min at 86%, 5.5-8.5 min at 86% B, 8.5-9 min at 84% B, 9-14 min at 84% B, 14-17 min at 80% B, 17-23 min at 60% B, 23-26 min at 60% B, 26-27 min at 95% B, and 27-35 min at 95% B
Flow Rate:	0.25 mL/min
Solvent A:	90% Water/10% Acetonitrile; 10 mM ammonium acetate pH 9.0 with ammonia; 2.5 μM InfinityLab Deactivator Additive
Solvent B:	85% Acetonitrile/15% Water; 10 mM Ammonium acetate pH 9.0 with ammonia; 2.5 μM InfinityLab Deactivator Additive
Chromatography Type:	HILIC

Analysis:

Analysis ID:	AN007116
Analysis Type:	MS
Chromatography ID:	CH005406
Num Factors:	3
Num Metabolites:	4
Units:	peak area