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Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [CXCR4]

ABSTRACT: Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [CXCR4]

PROVIDER: PRJNA587131 | ENA |

REPOSITORIES: ENA

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Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [CXCR4]

Project description: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.

2022-02-14 | GSE139838 | GEO

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [HE]

2022-02-14 | GSE139843 | GEO

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [scRNA-seq]

2022-02-14 | GSE139850 | GEO

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells

Project description:Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells

| PRJNA587143 | ENA

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [HE]

Project description:Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [HE]

| PRJNA587137 | ENA

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [scRNA-seq]

Project description:Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [scRNA-seq]

| PRJNA587149 | ENA

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-14 | GSE139853 | GEO

Common primitive-definitive hematopoietic precursors vs. Definitve hematopoietic progenitor cells

Project description:Transcriptional profiling of mouse ES cell-derived hemaopoitic cells comparing common primitive-definitive hematopoietic precursors (CD41SP) with definitve hematopoietic progenitor cells (KA45)

2013-11-27 | GSE48189 | GEO

Common primitive-definitive hematopoietic precursors vs. Definitve hematopoietic progenitor cells

2013-11-27 | E-GEOD-48189 | biostudies-arrayexpress

Characterization and generation of human definitive multipotent hematopoietic stem/progenitor cells

Project description:Definitive hematopoiesis generates hematopoietic stem/progenitor cells (HSPCs) that give rise to all mature blood and immune cells, but remains poorly defined in human. Here, we resolve human hematopoietic populations at the earliest hematopoiesis stage by single-cell RNA-seq. We characterize the distinct molecular profiling between early primitive and definitive hematopoiesis in both human embryonic stem cell (hESC) differentiation and early embryonic development. We generate definitive HSPCs from hESCs that hold the multipotency to differentiate various blood and immune cells, as validated by single-cell clonal assay. Strikingly, the generated HSPCs from hESCs give rise to various blood and lymphoid lineages in vivo. Lastly, we characterize gene-expression dynamics in definitive and primitive hematopoiesis and reveal an unreported role of ROCK-inhibition in enhancing human definitive hematopoiesis. Our study provides a prospect for understanding human early hematopoiesis and a firm basis to generate blood and immune cells for clinical purposes.

2020-12-09 | GSE148215 | GEO

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