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NOTO directs hIPSC-derived mesendoderm progenitors to a notochordal fate

ABSTRACT: NOTO transcription factor directs human induced pluripotent stem cell-derived mesendoderm progenitors to a notochordal fate

PROVIDER: PRJEB36475 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR3852350.fastq.gz	Fastqsanger.gz
	ERR3852360.fastq.gz	Fastqsanger.gz
	ERR3852370.fastq.gz	Fastqsanger.gz
	ERR3852351.fastq.gz	Fastqsanger.gz
	ERR3852361.fastq.gz	Fastqsanger.gz

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RNA-seq analysis of the impact of intermediate passaging on cell fate determination of mesendoderm progenitors

Project description:To investigate the impact of intermediate passaging on cell fate determination, cells were passaged during mesendoderm differentiation, and samples collected at different time points were subjected to bulk RNA-seq. We report here that intermediate passaging alters cell fate and directs mesendodermal progenitors toward cardiac cell fate.

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TBX3 Directs Cell-Fate Decision toward Mesendoderm.

Project description:Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

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NOTO Transcription Factor Directs Human Induced Pluripotent Stem Cell-Derived Mesendoderm Progenitors to a Notochordal Fate.

Project description:The founder cells of the Nucleus pulposus, the centre of the intervertebral disc, originate in the embryonic notochord. After birth, mature notochordal cells (NC) are identified as key regulators of disc homeostasis. Better understanding of their biology has great potential in delaying the onset of disc degeneration or as a regenerative-cell source for disc repair. Using human pluripotent stem cells, we developed a two-step method to generate a stable NC-like population with a distinct molecular signature. Time-course analysis of lineage-specific markers shows that WNT pathway activation and transfection of the notochord-related transcription factor NOTO are sufficient to induce high levels of mesendoderm progenitors and favour their commitment toward the notochordal lineage instead of paraxial and lateral mesodermal or endodermal lineages. This study results in the identification of NOTO-regulated genes including some that are found expressed in human healthy disc tissue and highlights NOTO function in coordinating the gene network to human notochord differentiation.

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