HCA Data Explorer

Combinatorial transcription factor profiles predict mature and functional human islet α and β cells

Updated September 16, 2022

Single cell RNAseq data of human pancreatic islets from 5 non-diabetic donors. Project abstract: Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled >40,000 cells from normal human islets by scRNA-seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells co-expressing ARX/MAFB (α cells) and MAFA/MAFB (β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-seq, MAFA/MAFB co-expressing β cells showed enhanced electrophysiological activity. Thus, these results indicate combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.

Jean-Philippe CartaillerVanderbilt Center for Stem Cell Biologyjp.cartailler@vanderbilt.edu
Marcela BrissovaVanderbilt University Medical Centermarcela.brissova@Vanderbilt.edu
Shristi Shrestha (Computational Scientist)1
Diane C Saunders (Experimental Scientist)1
John T Walker (Experimental Scientist)2
Joan Camunas-Soler3
Xiao-Qing Dai4
Rachana Haliyur2
Radhika Aramandla1
Greg Poffenberger1
Nripesh Prasad5
Rita Bottino6
Roland Stein2
Stephen Cj Parker7
Patrick E MacDonald4
Shawn E Levy5
Alvin C Powers1
Jean-Philippe Cartailler (Computational Scientist)8
Marcela Brissova (Principal Investigator)1
1Vanderbilt University Medical Center
2Vanderbilt University School of Medicine
3Stanford University
4University of Alberta
5HudsonAlpha Institute for Biotechnology
6Imagine Pharma
7University of Michigan
8Vanderbilt Center for Stem Cell Biology
Parisa Nejad
Rachel Schwartz
Brittney D Wick

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/daa371e8-1ec3-43ef-924f-896d901eab6f

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://powersbrissovalab.shinyapps.io/scRNAseq-Islets/
GEO Series Accessions:INSDC Project Accessions:INSDC Study Accessions:

For information regarding data sharing and data use, please see our Data Access Policy.

Analysis Portals

None

Project Label

scHumanPancreaticIslets

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

pancreas

Organ Part

islet of Langerhans

Selected Cell Types

10 cell types

Disease Status (Specimen)

normal

Disease Status (Donor)

normal

Development Stage

2 development stages

Library Construction Method

10x 3' v2

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

analysis_protocol_1

File Format

3 file formats

Cell Count Estimate

45.0k

Donor Count

5
fastq.gz168 file(s)txt.gz3 file(s)xlsx1 file(s)