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Universal principles of lineage architecture and stem cell identity in renewing tissues

Universal principles of lineage architecture and stem cell identity in renewing tissues
Universal principles of lineage architecture and stem cell identity in renewing tissues
Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover and repair. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship be- tween cell molecular ‘states’ (patterns of gene, protein expression etc. in the cell) and cell ‘types’ that uses notions from network science to decompose the structure of cell state trajectories into functional units. Using this framework we show that many widely experimentally observed features of cell lineage architectures – including the fact that a single adult stem cell type always resides at the apex of a lineage hi- erarchy – arise as a natural consequence of homeostasis, and indeed are the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment. Thus, we argue that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic, characteristics.
Cell state, Cell trajectories, Cell type, Self-renewal, Stem cell fate choice, Stem cell lineage
1477-9129
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Macarthur, Benjamin
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Parigini, Cristina
e703096b-49c9-43e6-af7c-62a3a85e9a9b
Sanchez Garcia, Ruben
8246cea2-ae1c-44f2-94e9-bacc9371c3ed
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Macarthur, Benjamin
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Parigini, Cristina
e703096b-49c9-43e6-af7c-62a3a85e9a9b
Sanchez Garcia, Ruben
8246cea2-ae1c-44f2-94e9-bacc9371c3ed

Greulich, Philip, Macarthur, Benjamin, Parigini, Cristina and Sanchez Garcia, Ruben (2021) Universal principles of lineage architecture and stem cell identity in renewing tissues. Development, 148 (11), [dev194399].

Record type: Article

Abstract

Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover and repair. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship be- tween cell molecular ‘states’ (patterns of gene, protein expression etc. in the cell) and cell ‘types’ that uses notions from network science to decompose the structure of cell state trajectories into functional units. Using this framework we show that many widely experimentally observed features of cell lineage architectures – including the fact that a single adult stem cell type always resides at the apex of a lineage hi- erarchy – arise as a natural consequence of homeostasis, and indeed are the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment. Thus, we argue that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic, characteristics.

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More information

Submitted date: 10 March 2020
Accepted/In Press date: 1 April 2021
Published date: 8 June 2021
Keywords: Cell state, Cell trajectories, Cell type, Self-renewal, Stem cell fate choice, Stem cell lineage

Identifiers

Local EPrints ID: 438726
URI: http://eprints.soton.ac.uk/id/eprint/438726
ISSN: 1477-9129
PURE UUID: 674f8266-c03d-4811-b4fa-8fa10d7093d3
ORCID for Philip Greulich: ORCID iD orcid.org/0000-0001-5247-6738
ORCID for Ruben Sanchez Garcia: ORCID iD orcid.org/0000-0001-6479-3028

Catalogue record

Date deposited: 23 Mar 2020 17:31
Last modified: 26 Nov 2021 03:01

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