p57Kip2 imposes the reserve stem cell state of gastric chief cells

Ji Hyun Lee; Somi Kim; Seungmin Han; Jimin Min; Brianna Caldwell; Aileen Diane Bamford; Andreia Sofia Batista Rocha; Jin Young Park; Sieun Lee; Szu Hsien Sam Wu; Heetak Lee; Juergen Fink; Sandra Pilat-Carotta; Jihoon Kim; Manon Josserand; Réka Szep-Bakonyi; Yohan An; Young Seok Ju; Anna Philpott; Benjamin D. Simons; Daniel E. Stange; Eunyoung Choi; Bon Kyoung Koo; Jong Kyoung Kim

doi:10.1016/j.stem.2022.04.001

p57^Kip2 imposes the reserve stem cell state of gastric chief cells

Ji Hyun Lee, Somi Kim, Seungmin Han, Jimin Min, Brianna Caldwell, Aileen Diane Bamford, Andreia Sofia Batista Rocha, Jin Young Park, Sieun Lee, Szu Hsien Sam Wu, Heetak Lee, Juergen Fink, Sandra Pilat-Carotta, Jihoon Kim, Manon Josserand, Réka Szep-Bakonyi, Yohan An, Young Seok Ju, Anna Philpott, Benjamin D. SimonsDaniel E. Stange, Eunyoung Choi, Bon Kyoung Koo, Jong Kyoung Kim

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Adult stem cells constantly react to local changes to ensure tissue homeostasis. In the main body of the stomach, chief cells produce digestive enzymes; however, upon injury, they undergo rapid proliferation for prompt tissue regeneration. Here, we identified p57^Kip2 (p57) as a molecular switch for the reserve stem cell state of chief cells in mice. During homeostasis, p57 is constantly expressed in chief cells but rapidly diminishes after injury, followed by robust proliferation. Both single-cell RNA sequencing and dox-induced lineage tracing confirmed the sequential loss of p57 and activation of proliferation within the chief cell lineage. In corpus organoids, p57 overexpression induced a long-term reserve stem cell state, accompanied by altered niche requirements and a mature chief cell/secretory phenotype. Following the constitutive expression of p57 in vivo, chief cells showed an impaired injury response. Thus, p57 is a gatekeeper that imposes the reserve stem cell state of chief cells in homeostasis.

Original language	English (US)
Pages (from-to)	826-839.e9
Journal	Cell Stem Cell
Volume	29
Issue number	5
DOIs	https://doi.org/10.1016/j.stem.2022.04.001
State	Published - May 5 2022
Externally published	Yes

Keywords

base stem cells
gastric chief cells
Gif
Lgr5
p57
reserve stem cells
scRNA-seq
stem cell quiescence
stomach
Troy

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

Access to Document

10.1016/j.stem.2022.04.001

Cite this

Lee, J. H., Kim, S., Han, S., Min, J., Caldwell, B., Bamford, A. D., Rocha, A. S. B., Park, J. Y., Lee, S., Wu, S. H. S., Lee, H., Fink, J., Pilat-Carotta, S., Kim, J., Josserand, M., Szep-Bakonyi, R., An, Y., Ju, Y. S., Philpott, A., ... Kim, J. K. (2022). p57^Kip2 imposes the reserve stem cell state of gastric chief cells. Cell Stem Cell, 29(5), 826-839.e9. https://doi.org/10.1016/j.stem.2022.04.001

Lee, JH, Kim, S, Han, S, Min, J, Caldwell, B, Bamford, AD, Rocha, ASB, Park, JY, Lee, S, Wu, SHS, Lee, H, Fink, J, Pilat-Carotta, S, Kim, J, Josserand, M, Szep-Bakonyi, R, An, Y, Ju, YS, Philpott, A, Simons, BD, Stange, DE, Choi, E, Koo, BK & Kim, JK 2022, 'p57^Kip2 imposes the reserve stem cell state of gastric chief cells', Cell Stem Cell, vol. 29, no. 5, pp. 826-839.e9. https://doi.org/10.1016/j.stem.2022.04.001

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abstract = "Adult stem cells constantly react to local changes to ensure tissue homeostasis. In the main body of the stomach, chief cells produce digestive enzymes; however, upon injury, they undergo rapid proliferation for prompt tissue regeneration. Here, we identified p57Kip2 (p57) as a molecular switch for the reserve stem cell state of chief cells in mice. During homeostasis, p57 is constantly expressed in chief cells but rapidly diminishes after injury, followed by robust proliferation. Both single-cell RNA sequencing and dox-induced lineage tracing confirmed the sequential loss of p57 and activation of proliferation within the chief cell lineage. In corpus organoids, p57 overexpression induced a long-term reserve stem cell state, accompanied by altered niche requirements and a mature chief cell/secretory phenotype. Following the constitutive expression of p57 in vivo, chief cells showed an impaired injury response. Thus, p57 is a gatekeeper that imposes the reserve stem cell state of chief cells in homeostasis.",

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AU - Lee, Ji Hyun

AU - Kim, Somi

AU - Han, Seungmin

AU - Min, Jimin

AU - Caldwell, Brianna

AU - Bamford, Aileen Diane

AU - Rocha, Andreia Sofia Batista

AU - Park, Jin Young

AU - Lee, Sieun

AU - Wu, Szu Hsien Sam

AU - Lee, Heetak

AU - Fink, Juergen

AU - Pilat-Carotta, Sandra

AU - Kim, Jihoon

AU - Josserand, Manon

AU - Szep-Bakonyi, Réka

AU - An, Yohan

AU - Ju, Young Seok

AU - Philpott, Anna

AU - Simons, Benjamin D.

AU - Stange, Daniel E.

AU - Choi, Eunyoung

AU - Koo, Bon Kyoung

AU - Kim, Jong Kyoung

PY - 2022/5/5

Y1 - 2022/5/5

N2 - Adult stem cells constantly react to local changes to ensure tissue homeostasis. In the main body of the stomach, chief cells produce digestive enzymes; however, upon injury, they undergo rapid proliferation for prompt tissue regeneration. Here, we identified p57Kip2 (p57) as a molecular switch for the reserve stem cell state of chief cells in mice. During homeostasis, p57 is constantly expressed in chief cells but rapidly diminishes after injury, followed by robust proliferation. Both single-cell RNA sequencing and dox-induced lineage tracing confirmed the sequential loss of p57 and activation of proliferation within the chief cell lineage. In corpus organoids, p57 overexpression induced a long-term reserve stem cell state, accompanied by altered niche requirements and a mature chief cell/secretory phenotype. Following the constitutive expression of p57 in vivo, chief cells showed an impaired injury response. Thus, p57 is a gatekeeper that imposes the reserve stem cell state of chief cells in homeostasis.

AB - Adult stem cells constantly react to local changes to ensure tissue homeostasis. In the main body of the stomach, chief cells produce digestive enzymes; however, upon injury, they undergo rapid proliferation for prompt tissue regeneration. Here, we identified p57Kip2 (p57) as a molecular switch for the reserve stem cell state of chief cells in mice. During homeostasis, p57 is constantly expressed in chief cells but rapidly diminishes after injury, followed by robust proliferation. Both single-cell RNA sequencing and dox-induced lineage tracing confirmed the sequential loss of p57 and activation of proliferation within the chief cell lineage. In corpus organoids, p57 overexpression induced a long-term reserve stem cell state, accompanied by altered niche requirements and a mature chief cell/secretory phenotype. Following the constitutive expression of p57 in vivo, chief cells showed an impaired injury response. Thus, p57 is a gatekeeper that imposes the reserve stem cell state of chief cells in homeostasis.

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