Stage specific reprogramming of mouse embryo liver cells to a beta cell-like phenotype

Yang, Ying; Akinci, Ersin; Dutton, James R.; Banga, Anannya; Slack, Jonathan

doi:10.1016/j.mod.2013.08.002

Cited by 22 publications

(10 citation statements)

References 51 publications

(71 reference statements)

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“…4b). To determine whether VE descendants attained transcriptional equivalence with DE descendants, we compared the expression of markers of the emergent endodermal organs within both populations: Nkx2–1 (thyroid/thymus) 41 , Irx1 (lung) 42 , Ppy (liver) 43 , Pdx1 (pancreas) 44 , Fabp1 (small intestine) 45 and Hoxb9 (posterior). All genes were expressed at substantial levels in both VE and DE cells, and at comparable AP positions, except for Nkx2–1 , which is expressed in the anterior-most cells of the gut tube and therefore exclusive to DE (Fig.…”

Section: Resultsmentioning

confidence: 99%

The emergent landscape of the mouse gut endoderm at single-cell resolution

Nowotschin

Setty

Kuo

et al. 2019

Nature

321

452

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Summary To delineate the ontogeny of the mammalian endoderm, we generated 112,217 single-cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. By employing graph-based approaches, we modelled differentiating cells for spatio-temporal characterization of developmental trajectories and defined the transcriptional architecture that accompanies the emergence of the first (primitive or extra-embryonic) endodermal population and its sister pluripotent (embryonic) epiblast lineage. We uncovered a relationship between descendants of these two lineages, whereby epiblast cells differentiate into endoderm at two distinct time-points, before and during gastrulation. Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates, and as they spatially converged within the nascent gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observed the regionalized identity of cells along the anterior-posterior axis of the emergent gut tube, reflecting their embryonic or extra-embryonic origin, and their coordinate patterning into organ-specific territories.

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Section: Resultsmentioning

confidence: 99%

The emergent landscape of the mouse gut endoderm at single-cell resolution

Nowotschin

Setty

Kuo

et al. 2019

Nature

321

452

View full text Add to dashboard Cite

show abstract

“…5b). To determine if VE cells, being of extra-embryonic origin, attained a level of equivalence to DE descendants, we compared the expression of markers of the primordial endodermal organs within the two populations: Nkx2-1 (thyroid/thymus) 61 , Irx1 (lung) 62 , Ppy (liver) 63 , Pdx1 (pancreas) 64 , Fabp1 (small intestine) 65 and Hoxb9 (posterior). With the exception of Nkx2-1, which is expressed in the anterior-most cells of the gut tube and is therefore exclusive to DE, all other genes were expressed at significant levels in both VE and DE cells, and at similar AP positions (Fig.…”

Section: Ap Patterning Occurs Concomitant With the Formation Of The Gmentioning

confidence: 99%

Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution

Nowotschin

Setty

Kuo

et al. 2018

Preprint

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words)To comprehensively delineate the ontogeny of an organ system, we generated 112,217 singlecell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatiotemporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.

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“…One TF, Pdx1, could convert 0.3% to 6% of transduced hepatocytes (which start with the same endodermal lineage) to insulin secreting cells (Ferber et al, 2000), but adding other TFs (NeuroD, Ngn3/betacellulin, Mafa, and Pax4) substantially enhanced the conversion efficiency (Berneman-Zeitouni et al, 2014; Yang et al, 2013). In contrast, pancreatic non-β-cells, like acinar cells, are closer to the β-cell lineage and more advantageous to be converted.…”

Section: Regeneration In Non-mammalian Vertebrates and Other Mammamentioning

confidence: 99%

Cochlear hair cell regeneration after noise-induced hearing loss: Does regeneration follow development?

Zheng

Zuo

2017

Hearing Research

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Noise-induced hearing loss (NIHL) affects a large number of military personnel and civilians. Regenerating inner-ear cochlear hair cells (HCs) is a promising strategy to restore hearing after NIHL. In this review, we first summarize recent transcriptome profile analysis of zebrafish lateral lines and chick utricles where spontaneous HC regeneration occurs after HC damage. We then discuss recent studies in other mammalian regenerative systems such as pancreas, heart and central nervous system. Both spontaneous and forced HC regeneration occurs in mammalian cochleae in vivo involving proliferation and direct lineage conversion. However, both processes are inefficient and incomplete, and decline with age. For direct lineage conversion in vivo in cochleae and in other systems, further improvement requires multiple factors, including transcription, epigenetic and trophic factors, with appropriate stoichiometry in appropriate architectural niche. Increasing evidence from other systems indicates that the molecular paths of direct lineage conversion may be different from those of normal developmental lineages. We therefore hypothesize that HC regeneration does not have to follow HC development and that epigenetic memory of supporting cells influences the HC regeneration, which may be a key to successful cochlear HC regeneration. Finally, we discuss recent efforts in viral gene therapy and drug discovery for HC regeneration. We hope that combination therapy targeting multiple factors and epigenetic signaling pathways will provide promising avenues for HC regeneration in humans with NIHL and other types of hearing loss.

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Stage specific reprogramming of mouse embryo liver cells to a beta cell-like phenotype

Cited by 22 publications

References 51 publications

The emergent landscape of the mouse gut endoderm at single-cell resolution

The emergent landscape of the mouse gut endoderm at single-cell resolution

Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution

Cochlear hair cell regeneration after noise-induced hearing loss: Does regeneration follow development?

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