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| Status |
Public on Feb 14, 2022 |
| Title |
Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [scRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The generation of the hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is a major goal for regenerative medicine. HSCs derive from hemogenic endothelium (HE) in a retinoic acid (RA)-dependent manner1. While a WNT-dependent (WNTd) patterning of nascent mesoderm specifies clonally multipotent definitive HE from hPSCs2,3, this HE is functionally unresponsive to RA4. Here we show that WNTd mesoderm, prior to HE specification, is comprised of two distinct KDR+CD34negT+ populations. In a TGFb-independent manner, CXCR4negCYP26A1+ mesoderm is specified, which gives rise to HOXA+ multilineage definitive HE, in an RA-independent manner. In contrast, CXCR4+ALDH1A2+ mesoderm is specified in a TGFb-dependent manner, and gives rise to multilineage definitive HE in a stage-specific, RA-dependent manner. Further, this NOTCH-dependent HE harbored HOXA expression resembling fetal HE. This model of human hematopoietic development defines the mesodermal origins of multiple waves of hematopoiesis, and that RA-dependent hematopoietic development occurs prior to HE development.
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| Overall design |
Whole day 3 embroid bodies (EBs) from WNTi (IWP2 + ACTIVIN A) and WNTd (CHIR99021 + SB43152) were harvest and processed using the 10X platform.
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| Contributor(s) |
Luff SA, Creamer JP, Valsoni S, Dege C, Scarfo R, Dacunto A, Merelli I, Morris S, Ditadi A, Sturgeon CM |
| Citation(s) |
35569347 |
| Submission date |
Nov 01, 2019 |
| Last update date |
Jul 07, 2022 |
| Contact name |
Stephanie Luff |
| E-mail(s) |
stephanie.luff@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Cell, Developmental, & Regenerative Biology
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| Lab |
Sturgeon
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| Street address |
1425 Madison Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE139853 |
Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells |
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| Relations |
| BioProject |
PRJNA587149 |
| SRA |
SRP227988 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE139850_counts_matrix.txt.gz |
42.9 Mb |
(ftp)(http) |
TXT |
| GSE139850_metadata.txt.gz |
239.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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