Abstract
| Original language | English |
|---|---|
| Article number | 5187 |
| Journal | Nature communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2022 |
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In: Nature communications, Vol. 13, No. 1, 5187, 01.12.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity
AU - Kim, Kyung Mok
AU - Mura-Meszaros, Anna
AU - Tollot, Marie
AU - Krishnan, Murali Shyam
AU - Gründl, Marco
AU - Neubert, Laura
AU - Groth, Marco
AU - Rodriguez-Fraticelli, Alejo
AU - Svendsen, Arthur Flohr
AU - Campaner, Stefano
AU - Andreas, Nico
AU - Kamradt, Thomas
AU - Hoffmann, Steve
AU - Camargo, Fernando D.
AU - Heidel, Florian H.
AU - Bystrykh, Leonid V.
AU - de Haan, Gerald
AU - von Eyss, Björn
N1 - Funding Information: B.v.E. was supported by grants from the DFG (EY 120/1-1), Else Kröner-Fresenius Foundation (2016_A58) and the German Cancer Aid (Deutsche Krebshilfe; 70113138). The FLI is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. F.H.H. was supported in part by grants of the German Research Council (DFG), (HE6233/4-1 and 4-2) and by the Thuringian state program ProExzellenz (RegenerAging - FSU-I-03/14) of the Thuringian Ministry for Economics, Science and Digital Society (TMWWDG). G.d.H. was supported by the Landsteiner Foundation for Blood Transfusion Research. A.E.R.-F. is a Special Fellow of the Leukemia and Lymphoma Society (3391-19). A.E.R.-F. received the support of a fellowship from ”la Caixa” Foundation (ID 100010434) and from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 847648. The fellowship code is LCF/BQ/ES08/11520137. BM-HPC#5 cells were a kind gift from Leif Carlsson. The DNA Sequencing and the Flow Cytometry and the of the FLI are gratefully acknowledged. We would like to thank all the members of the von Eyss lab, von Maltzahn lab, Rudolph lab, and Kaether lab for helpful discussion and Christin Ritter and Tom Hünniger and all the animal care takers at FLI for excellent technical support. Some of the figures were created with BioRender.com. Funding Information: B.v.E. was supported by grants from the DFG (EY 120/1-1), Else Kröner-Fresenius Foundation (2016_A58) and the German Cancer Aid (Deutsche Krebshilfe; 70113138). The FLI is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. F.H.H. was supported in part by grants of the German Research Council (DFG), (HE6233/4-1 and 4-2) and by the Thuringian state program ProExzellenz (RegenerAging - FSU-I-03/14) of the Thuringian Ministry for Economics, Science and Digital Society (TMWWDG). G.d.H. was supported by the Landsteiner Foundation for Blood Transfusion Research. A.E.R.-F. is a Special Fellow of the Leukemia and Lymphoma Society (3391-19). A.E.R.-F. received the support of a fellowship from ”la Caixa” Foundation (ID 100010434) and from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 847648. The fellowship code is LCF/BQ/ES08/11520137. BM-HPC#5 cells were a kind gift from Leif Carlsson. The DNA Sequencing and the Flow Cytometry and the of the FLI are gratefully acknowledged. We would like to thank all the members of the von Eyss lab, von Maltzahn lab, Rudolph lab, and Kaether lab for helpful discussion and Christin Ritter and Tom Hünniger and all the animal care takers at FLI for excellent technical support. Some of the figures were created with BioRender.com. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, as we age, the immune system shows a functional decline that can be attributed in large part to age-associated defects in hematopoietic stem cells (HSCs)—the cells at the apex of the immune cell hierarchy. Here, we find that the Hippo pathway coactivator TAZ is potently induced in old HSCs and protects these cells from functional decline. We identify Clca3a1 as a TAZ-induced gene that allows us to trace TAZ activity in vivo. Using CLCA3A1 as a marker, we can isolate “young-like” HSCs from old mice. Mechanistically, Taz acts as coactivator of PU.1 and to some extent counteracts the gradual loss of PU.1 expression during HSC aging. Our work thus uncovers an essential role for Taz in a previously undescribed fail-safe mechanism in aging HSCs.
AB - Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, as we age, the immune system shows a functional decline that can be attributed in large part to age-associated defects in hematopoietic stem cells (HSCs)—the cells at the apex of the immune cell hierarchy. Here, we find that the Hippo pathway coactivator TAZ is potently induced in old HSCs and protects these cells from functional decline. We identify Clca3a1 as a TAZ-induced gene that allows us to trace TAZ activity in vivo. Using CLCA3A1 as a marker, we can isolate “young-like” HSCs from old mice. Mechanistically, Taz acts as coactivator of PU.1 and to some extent counteracts the gradual loss of PU.1 expression during HSC aging. Our work thus uncovers an essential role for Taz in a previously undescribed fail-safe mechanism in aging HSCs.
UR - http://www.scopus.com/inward/record.url?scp=85137155076&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-022-32970-1
DO - https://doi.org/10.1038/s41467-022-32970-1
M3 - Article
C2 - 36057685
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5187
ER -