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Page 1
Aging of intestinal stem cells.
Nalapareddy K, Zheng Y, Geiger H. Nalapareddy K, et al. Stem Cell Reports. 2022 Apr 12;17(4):734-740. doi: 10.1016/j.stemcr.2022.02.003. Epub 2022 Mar 10. Stem Cell Reports. 2022. PMID: 35276089 Free PMC article. Review.
Cdc42-Borg4-Septin7 axis regulates HSC polarity and function.
Kandi R, Senger K, Grigoryan A, Soller K, Sakk V, Schuster T, Eiwen K, Menon MB, Gaestel M, Zheng Y, Florian MC, Geiger H. Kandi R, et al. EMBO Rep. 2021 Dec 6;22(12):e52931. doi: 10.15252/embr.202152931. Epub 2021 Oct 18. EMBO Rep. 2021. PMID: 34661963 Free PMC article.
Aging of hematopoietic stem cells (HSCs) is caused by the elevated activity of the small RhoGTPase Cdc42 and an apolar distribution of proteins. Mechanisms by which Cdc42 activity controls polarity of HSCs are not known. ...Here, we show that Cdc42 interacts …
Aging of hematopoietic stem cells (HSCs) is caused by the elevated activity of the small RhoGTPase Cdc42 and an apolar distribution o …
Cdc42 and aging of hematopoietic stem cells.
Geiger H, Zheng Y. Geiger H, et al. Curr Opin Hematol. 2013 Jul;20(4):295-300. doi: 10.1097/MOH.0b013e3283615aba. Curr Opin Hematol. 2013. PMID: 23615056 Free PMC article. Review.
Mouse model studies have found that aging is associated with elevated activity of the Rho GTPase Cdc42 in HSCs that is causative for loss of polarity, altered epigenetic modifications and functional deficits of aged HSCs. The work suggests that inhibition of Cdc42 a …
Mouse model studies have found that aging is associated with elevated activity of the Rho GTPase Cdc42 in HSCs that is causative for …
Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice.
Montserrat-Vazquez S, Ali NJ, Matteini F, Lozano J, Zhaowei T, Mejia-Ramirez E, Marka G, Vollmer A, Soller K, Sacma M, Sakk V, Mularoni L, Mallm JP, Plass M, Zheng Y, Geiger H, Florian MC. Montserrat-Vazquez S, et al. NPJ Regen Med. 2022 Dec 29;7(1):78. doi: 10.1038/s41536-022-00275-y. NPJ Regen Med. 2022. PMID: 36581635 Free PMC article.
Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mic …
Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplant …
Regulation of hematopoietic stem cell aging by the small RhoGTPase Cdc42.
Geiger H, Zheng Y. Geiger H, et al. Exp Cell Res. 2014 Dec 10;329(2):214-9. doi: 10.1016/j.yexcr.2014.09.001. Epub 2014 Sep 16. Exp Cell Res. 2014. PMID: 25220425 Free PMC article. Review.
In this review article, we introduce the canonical set of phenotypes associated with aged HSCs, focus on the novel aging-associated phenotype apolarity caused by elevated activity of the small RhoGTPase in aged HSCs, discuss the role of Cdc42 in hematopoiesis and describe …
In this review article, we introduce the canonical set of phenotypes associated with aged HSCs, focus on the novel aging-associated phenotyp …
Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells.
Nalapareddy K, Hassan A, Sampson LL, Zheng Y, Geiger H. Nalapareddy K, et al. iScience. 2021 Mar 26;24(4):102362. doi: 10.1016/j.isci.2021.102362. eCollection 2021 Apr 23. iScience. 2021. PMID: 33870147 Free PMC article.
We report that aged intestinal crypts present with an elevated activity of the small RhoGTPase Cdc42. Elevation of Cdc42 activity in young animals by genetic means causes premature ISC aging, whereas pharmacological suppression of elevated Cdc42 activity rest …
We report that aged intestinal crypts present with an elevated activity of the small RhoGTPase Cdc42. Elevation of Cdc42 activ …
Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity.
Amoah A, Keller A, Emini R, Hoenicka M, Liebold A, Vollmer A, Eiwen K, Soller K, Sakk V, Zheng Y, Florian MC, Geiger H. Amoah A, et al. Haematologica. 2022 Feb 1;107(2):393-402. doi: 10.3324/haematol.2020.269670. Haematologica. 2022. PMID: 33440922 Free PMC article.
The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect …
The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 act …
Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice.
Florian MC, Leins H, Gobs M, Han Y, Marka G, Soller K, Vollmer A, Sakk V, Nattamai KJ, Rayes A, Zhao X, Setchell K, Mulaw M, Wagner W, Zheng Y, Geiger H. Florian MC, et al. Aging Cell. 2020 Sep;19(9):e13208. doi: 10.1111/acel.13208. Epub 2020 Aug 4. Aging Cell. 2020. PMID: 32755011 Free PMC article.
Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain-of-activity mouse model presents with a premature aging-like phenotype and with
Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated
Rational identification of a Cdc42 inhibitor presents a new regimen for long-term hematopoietic stem cell mobilization.
Liu W, Du W, Shang X, Wang L, Evelyn C, Florian MC, A Ryan M, Rayes A, Zhao X, Setchell K, Meller J, Guo F, Nassar N, Geiger H, Pang Q, Zheng Y. Liu W, et al. Leukemia. 2019 Mar;33(3):749-761. doi: 10.1038/s41375-018-0251-5. Epub 2018 Sep 25. Leukemia. 2019. PMID: 30254339 Free PMC article.
Here we rationally identified a Cdc42 activity-specific inhibitor (CASIN) that can bind to Cdc42 with submicromolar affinity and competitively interfere with guanine nucleotide exchange activity. CASIN inhibits intracellular Cdc42 activity specifically and tr …
Here we rationally identified a Cdc42 activity-specific inhibitor (CASIN) that can bind to Cdc42 with submicromolar affinity a …
An aged bone marrow niche restrains rejuvenated hematopoietic stem cells.
Guidi N, Marka G, Sakk V, Zheng Y, Florian MC, Geiger H. Guidi N, et al. Stem Cells. 2021 Aug;39(8):1101-1106. doi: 10.1002/stem.3372. Epub 2021 Apr 13. Stem Cells. 2021. PMID: 33847429 Free article.
An increase in the activity of the small RhoGTPase cell division control protein 42 (Cdc42) within HSCs causes aging of HSCs. Old HSCs, treated ex vivo with a specific inhibitor of Cdc42 activity termed CASIN, stay rejuvenated upon transplantation into young recipie …
An increase in the activity of the small RhoGTPase cell division control protein 42 (Cdc42) within HSCs causes aging of HSCs. Old HSC …
19 results