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Generation of E9.0 mouse embryonic progenitors

ABSTRACT: Multipotent Nkx2-1-positive lung epithelial primordial progenitors of the foregut endoderm are thought to be the developmental precursors to all adult lung epithelial lineages. However, little is known about the global transcriptomic programs or gene networks that regulate these gateway progenitors in vivo due to their rarity and transient presence during a narrow developmental window, embryonic day E9.0 in mice. Here we describe the unique genetic program of in vivo lung primordial progenitors and computationally identify the signaling pathways that are involved in their cell-fate determination from pre-specified embryonic foregut. We integrate this information in computational models to generate in vitro engineered lung primordial progenitors from mouse pluripotent stem cells, improving the fidelity of the resulting cells through unbiased, easy-to-interpret similarity scores and modulation of cell culture conditions, including biomechanical cues. As the genetic characterization of early in vivo embryonic progenitors is rapidly expanding, the methodology proposed here can have wide applicability to the in vitro derivation of bona fide tissue progenitors of all germ layers.

ORGANISM(S): Mus musculus

PROVIDER: GSE138904 | GEO | 2019/12/20

REPOSITORIES: GEO

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Early lineage commitment defines alveolar epithelial ontogeny in the lung (E13.5, E15.5 and E17.5)

Project description:Multipotent Nkx2-1-positive lung epithelial primordial progenitors of the foregut endoderm are thought to be the developmental precursors to all adult lung epithelial lineages. However, little is known about the global transcriptomic programs or gene networks that regulate these gateway progenitors in vivo due to their rarity and transient presence during a narrow developmental window, embryonic day E9.0 in mice. Here we describe the unique genetic program of in vivo lung primordial progenitors and computationally identify the signaling pathways that are involved in their cell-fate determination from pre-specified embryonic foregut. We integrate this information in computational models to generate in vitro engineered lung primordial progenitors from mouse pluripotent stem cells, improving the fidelity of the resulting cells through unbiased, easy-to-interpret similarity scores and modulation of cell culture conditions, including biomechanical cues. As the genetic characterization of early in vivo embryonic progenitors is rapidly expanding, the methodology proposed here can have wide applicability to the in vitro derivation of bona fide tissue progenitors of all germ layers.

2019-12-20 | GSE139186 | GEO

Generation of E9.0 mouse embryonic progenitors

Project description:Generation of E9.0 mouse embryonic progenitors

| PRJNA577710 | ENA

Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells

Project description:Two populations of Nkx2-1+ progenitors in the developing foregut endoderm give rise to the entire post-natal lung and thyroid epithelium, but little is known about these cells, as they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGFM-NM-2 and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1GFP knock-in reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development. Comparison between Nkx2-1 positive and Nkx2-1 negative cells derived after 14 days of differentiation of mouse ES cells carrying a knock-in reporter gene, Nkx2-1GFP.

2012-04-04 | E-GEOD-35063 | biostudies-arrayexpress

Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells

Project description:Two populations of Nkx2-1+ progenitors in the developing foregut endoderm give rise to the entire post-natal lung and thyroid epithelium, but little is known about these cells, as they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGFβ and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1GFP knock-in reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.

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Global gene expression kinetics of early human lung development modeled by directed differentiation of human PSCs using an NKX2-1GFP iPSC reporter

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2010-01-14 | E-GEOD-19873 | biostudies-arrayexpress

Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction.

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Gene expression in whole mouse E9.0 embryos comparing wt with Arid3b-null embryos

Project description:We have analysed and compared mRNA expression between wt embryos and embryos deficient for Arid3b at E9.0 days of development, with the aim of identifying differentially expressed genes that could give us a clue to the functions of Arid3b during development.

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Gene expression in whole mouse E9.0 embryos comparing wt with Arid3b-null embryos

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