Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells

Nabhan, Ahmad; Brownfield, Douglas; Harbury, Pehr B.; Krasnow, Mark A.; Desai, Tushar J.

doi:10.1126/science.aam6603

Cited by 595 publications

(757 citation statements)

References 63 publications

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“…One possibility is that, in common with the mouse adult trachea or developing lung, basal and luminal cells (viz. club cells in the trachea) act as a niche for each other, allowing the relative size of the compartments to achieve a stable equilibrium (Nabhan, Brownfield, Harbury, Krasnow, & Desai, 2018;Pardo-Saganta et al, 2015).…”

Section: Discussion and Per S Pec Tive Smentioning

confidence: 99%

Statistical theory of branching morphogenesis

Hannezo

Simons

2018

Dev Growth Differ

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Branching morphogenesis remains a subject of abiding interest. Although much is known about the gene regulatory programs and signaling pathways that operate at the cellular scale, it has remained unclear how the macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Lately, it has been proposed that, these features can be explained quantitatively in several organs within a single unifying framework. Based on large‐scale organ reconstructions and cell lineage tracing, it has been argued that morphogenesis follows from the collective dynamics of sublineage‐restricted self‐renewing progenitor cells, localized at ductal tips, that act cooperatively to drive a serial process of ductal elongation and stochastic tip bifurcation. By correlating differentiation or cell cycle exit with proximity to maturing ducts, this dynamic results in the specification of a complex network of defined density and statistical organization. These results suggest that, for several mammalian tissues, branched epithelial structures develop as a self‐organized process, reliant upon a strikingly simple, but generic, set of local rules, without recourse to a rigid and deterministic sequence of genetically programmed events. Here, we review the basis of these findings and discuss their implications.

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Section: Discussion and Per S Pec Tive Smentioning

confidence: 99%

Statistical theory of branching morphogenesis

Hannezo

Simons

2018

Dev Growth Differ

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“…Studies are still underway to fully characterize the stem cells that replenish AT2 cells during steady state and after alveolar injury [15,16]. Rare subsets of AT2 cells, including α6β4 + AT2 cells and Axin2 + AT2 cells, can generate AT2 cells after lung injury in mice [17,18]. Zacharias et al also described a Wnt-responsive alveolar epithelial progenitor in healthy human lungs [19].…”

Section: Stem/progenitor Cells That Generatementioning

confidence: 99%

Organoids as a Powerful Model for Respiratory Diseases

Liu

Wu²,

Sun³

et al. 2020

Stem Cells International

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Insults to the alveoli usually lead to inefficient gas exchange or even respiratory failure, which is difficult to model in animal studies. Over the past decade, stem cell-derived self-organizing three-dimensional organoids have emerged as a new avenue to recapitulate respiratory diseases in a dish. Alveolar organoids have improved our understanding of the mechanisms underlying tissue homeostasis and pathological alterations in alveoli. From this perspective, we review the state-of-the-art technology on establishing alveolar organoids from endogenous lung epithelial stem/progenitor cells or pluripotent stem cells, as well as the use of alveolar organoids for the study of respiratory diseases, including idiopathic pulmonary fibrosis, tuberculosis infection, and respiratory virus infection. We also discuss challenges that need to be overcome for future application of alveolar organoids in individualized medicine.

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“…The daughter cell closer to the fibroblast receives the Wnt5a signal and remains a type II cell with stem cell potential, while the other daughter cell differentiates into a type I cell. Inhibiting Wnt activity in type II cells caused them to differentiate into type I cells, while activating Wnt activity inhibited their ability to differentiate into type I cells …”

Section: A New Type Of Stem Cell To Regenerate the Lungmentioning

confidence: 99%

Adult stem cells and regenerative medicine—a symposium report

Cable¹,

Fuchs

Weissman

et al. 2019

Annals of the New York Academy of Sciences

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Adult stem cells are rare, undifferentiated cells found in all tissues of the body. Although normally kept in a quiescent, nondividing state, these cells can proliferate and differentiate to replace naturally dying cells within their tissue and to repair its wounds in response to injury. Due to their proliferative nature and ability to regenerate tissue, adult stem cells have the potential to treat a variety of degenerative diseases as well as aging. In addition, since stem cells are often thought to be the source of malignant tumors, understanding the mechanisms that keep their proliferative abilities in check can pave the way for new cancer therapies. While adult stem cells have had limited practical and clinical applications to date, several clinical trials of stem cell–based therapies are underway. This report details recent research presented at the New York Academy of Sciences on March 14, 2019 on understanding the factors that regulate stem cell activity and differentiation, with the hope of translating these findings into the clinic.

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Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells

Cited by 595 publications

References 63 publications

Statistical theory of branching morphogenesis

Statistical theory of branching morphogenesis

Organoids as a Powerful Model for Respiratory Diseases

Adult stem cells and regenerative medicine—a symposium report

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