 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 27, 2019 |
| Title |
SOX9+/PTF1A+ Cells Define the Tip Progenitor Cells of the Human Fetal Pancreas of the Second Trimester |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Significant progress has been made in recent years in characterizing human multipotent progenitor cells (hMPCs) of the early pancreas; however, the identity and persistence of these cells during the second trimester, after the initiation of branching morphogenesis, remain elusive. Additionally, studies on hMPCs have been hindered by few isolation methods that allow for the recovery of live cells. Here, we investigated the tip progenitor domain in the branched epithelium of human fetal pancreas between 13.5 and 17.5 gestational weeks by immunohistological staining. We also used a novel RNA‐based technology to isolate live cells followed by gene expression analyses. We identified cells co‐expressing SOX9 and PTF1A, two transcription factors known to be important for pancreatic MPCs, within the tips of the epithelium and observed a decrease in their proportions over time. Pancreatic SOX9+/PTF1A+ cells were enriched for MPC markers, including MYC and GATA6. These cells were proliferative and appeared active in branching morphogenesis and matrix remodeling, as evidenced by gene set enrichment analysis. We identified a hub of genes pertaining to the expanding tip progenitor niche, such as FOXF1, GLI3, TBX3, FGFR1, TGFBR2, ITGAV, ITGA2, and ITGB3. YAP1 of the Hippo pathway emerged as a highly enriched component within the SOX9+/PTF1A+ cells. Single‐cell RNA‐sequencing further corroborated the findings by identifying a cluster of SOX9+/PTF1A+ cells with multipotent characteristics. Based on these results, we propose that the SOX9+/PTF1A+ cells in the human pancreas are uncommitted MPC‐like cells that reside at the tips of the expanding pancreatic epithelium, directing self‐renewal and inducing pancreatic organogenesis.
|
| |
|
| Overall design |
Total RNAs were extracted individual cells obtained following dissociation of freshly obtained human fetal pancreas tissue.
|
| |
|
| Contributor(s) |
Villani V, Thornton ME, Zook HN, Crook CJ, Grubbs BH, Orlando G, De Filippo R, Ku HT, Perin L |
| Citation(s) |
31631582 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 DK099734 |
EX VIVO DIFFERENTIATION AND EXPANSION OF ADULT PANCREATIC COLONY-FORMING UNITS |
Beckman Research Institute of the City of Hope |
Hsun Teresa Ku |
| R21 HD090545 |
A novel approach for the isolation of multipotent pancreas progenitors |
CHILDREN'S HOSPITAL LOS ANGELES |
Laura Perin |
|
| Submission date |
Nov 26, 2019 |
| Last update date |
Dec 05, 2019 |
| Contact name |
Teresa Ku |
| E-mail(s) |
hku@coh.org
|
| Organization name |
City of Hope - Beckman Research Institute
|
| Department |
Translational Research and Cellular Therapeutics
|
| Street address |
1500 E Duarte Rd
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (1) |
|
| Relations |
| BioProject |
PRJNA592003 |
| SRA |
SRP233386 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141087_RAW.tar |
144.6 Mb |
(http)(custom) |
TAR (of CSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
