<i>Mov10</i> mitigates hematopoietic stem cell exhaustion under stress by modulating the <i>Camp</i>-mediated inflammatory pathway

Changlin Zhen; Junbing Pan; Wei Wang; Jiankun Fan; Yonghui Zhang; Dan Liu; Shiheng Zhang; Xiaohuan Huang; Yalan Xiao; Yu Hou; Xueya Zhao; Zhigang Li

doi:10.1016/j.jgg.2026.05.012

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2026 > Accepted Manuscript

PDF( 0 KB)

Mov10 mitigates hematopoietic stem cell exhaustion under stress by modulating the Camp-mediated inflammatory pathway

doi: 10.1016/j.jgg.2026.05.012

a. Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China;
b. Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Natural Drug Intervention in Aging Key Laboratory of Chongqing Education Commission of China, School of Basic Medical Sciences, Chongqing Three Gorges Medical College, Chongqing 404100, China;
c. Department of Clinical Laboratory, The Third Hospital of Mianyang, Sichuan Mental Health Center, Chongqing Medical University, Chongqing, 400016, China;
d. Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University, Chongqing 400016, China;
e. Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016

Funds:

This research was supported by the National Natural Science Foundation of China (82525057 and 82200123), the Natural Science Foundation of Chongqing, China (CSTB2024NSCQ-MSX0116 and CSTB2023NSCQ-MSX0280), the Special Program for High-level Talents at Chongqing Three Gorges Medical College (06020605008), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K202402706, KJQN202302711, and KJQN202102701), and a multidisciplinary interdisciplinary innovation team for the protection and utilization of authentic medicinal materials in the Three Gorges Reservoir Area (CXTD202303).

Received Date: 2026-05-15
Accepted Date: 2026-05-24
Rev Recd Date: 2026-05-23

Available Online: 2026-05-30

Abstract

Abstract

The integrity of hematopoietic stem cell (HSC) function is crucial for robust hematopoietic regeneration following stress. Inflammatory responses are pivotal drivers of HSC stress response, yet the precise modulation of inflammatory pathways remains incompletely defined. In this study, we identify the RNA helicase Mov10 as a negative regulator of stress-induced inflammatory pathways in HSC. Our study indicates that Mov10, which is critically required for HSC maintenance, is highly expressed in HSCs, and its loss adversely affects HSC fitness and survival during hematopoietic stress induced by bone marrow transplantation and irradiation (IR). Mechanistically, Mov10 mitigates excessive inflammatory activation to sustain HSC functional integrity during hematopoietic stress, primarily by enhancing the translation of CAMP, which inhibits the interaction between TNF-α and its receptor TNFR1 and suppresses NF-κB activation. Overall, our results imply that Mov10 plays a critical role in averting functional failure of hematopoiesis under stress, presenting viable paths for the therapeutic intervention of relevant diseases.
- Camp,
- Hematopoietic stem cell,
- Hematopoietic stress,
- Inflammation,
- Mov10

FullText(HTML)

References(58)

References

Bei, Y.H., Pan, L.L., Zhou, Q.L., Zhao, C.M., Xie, Y., Wu, C.F., Meng, X.M., Gu, H.Y., Xu, J.H., Zhou, L., et al., 2019. Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury. BMC MED. 17, 42.

Blanco-Melo, D., Venkatesh, S., Bieniasz, P.D., 2012. Intrinsic cellular defenses against human immunodeficiency viruses. Immunity 37, 399-411.

Bogeska, R., Mikecin, A.M., Kaschutnig, P., Fawaz, M., Buchler-Schaff, M., Le, D., Ganuza, M., Vollmer, A., Paffenholz, S.V., Asada, N., et al., 2022. Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell 29, 1273-1284.

Borges, L., Oliveira, V.K.P., Baik, J., Bendall, S.C., Perlingeiro, R.C.R., 2019. Serial transplantation reveals a critical role for endoglin in hematopoietic stem cell quiescence. Blood 133, 688-696.

Caiado, F., Pietras, E.M., & Manz, M.G., 2021. Inflammation as a regulator of hematopoietic stem cell function in disease and clonal selection. J. Exp. Med. 218, e20201541.

Chen, F., Lu, Y.K., Xu, Y., Chen, N.C., Yang, L.J., Zhong, X.Y., Zeng, H., Liu, Y.Y., Chen, Z.J., Zhang, Q., et al., 2024. Trim47 prevents hematopoietic stem cell exhaustion during stress by regulating the MAVS-mediated innate immune pathway. Nat. Commun. 15, 6787.

Chen, Z., Huo, D.W., Li, L., Liu, Z.L., Li, Z.G., Xu, S.N., Huang, Y.X., Wu, W.R., Zhou, C.F., Liu, Y.Y., et al., 2021. Nuclear DEK preserves hematopoietic stem cells potential via NCoR1/HDAC3-Akt1/2-mTOR axis. J. Exp. Med. 218, e20201974.

Clapes, T., Polyzou, A., Prater, P., Sagar, Morales-Hernandez, A., Ferrarini, M.G., Kehrer, N., Lefkopoulos, S., Bergo, V., Hummel, B., et al., 2021. Chemotherapy-induced transposable elements activate MDA5 to enhance hematopoietic regeneration. Nat. Cell. Biol. 23, 704-717.

Cuevas, R.A., Ghosh, A., Wallerath, C., Hornung, V., Coyne, C.B., Sarkar, S.N., 2016. MOV10 provides antiviral activity against RNA viruses by enhancing RIG-I-MAVS-independent IFN induction. J. Immunol. 196, 3877-3886.

Dutta, A., Yang, Y., Le, B.T., Zhang, Y.F., Abdel-Wahab, O., Zang, C.Z., Mohi, G., 2021. U2af1 is required for the survival and function of hematopoietic stem/progenitor cells. Leukemia 35, 2382-2398.

Fei, X., Chen, S.H., Li, L.Y., Xu, X.B., Wang, H., Ke, H.J., He, C., Xie, C., Wu, X.D., Liu, J.P., et al., 2025. Infection promotes M1 macrophage polarization and gastric inflammation by activation of the NLRP3 inflammasome via TNF/TNFR1 axis. Cell Commun. Signal. 23, 6.

Fu, K., Tian, S., Tan, H., Wang, C., Wang, H., Wang, M., Wang, Y., Chen, Z., Wang, Y., Yue, Q., et al., 2019. Biological and RNA regulatory function of MOV10 in mammalian germ cells. BMC Biol. 17, 39.

Garcia-Prat, L., Kaufmann, K.B., Schneiter, F., Voisin, V., Murison, A., Chen, J.,Chan-Seng-Yue, M., Gan, O.I., McLeod, J.L., Smith, S.A., et al., 2021. TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate. Cell Stem Cell 28, 1838-1850.

Gebert, L.F.R., MacRae, I.J., 2019. Regulation of microRNA function in animals. Nat. Rev. Mol. Cell. Biol. 20, 21-37.

Hajishengallis, G., Li, X.F., Chavakis, T., 2021. Immunometabolic control of hematopoiesis. Mol. Aspects. Med. 77, 100923.

He, N.H., Yang, Q., Li, Z.J., Guo, J.J., Kuang, C.M., Zhu, Y.H., Liu, X., Chen, X., Shi, F.M., Feng, X. L., et al., 2025. LGR4 promotes proliferation and homing via activation of the NF-κB signaling pathway in multiple myeloma. Int. J. Oncol. 66, 12.

Hou, S., Liu, J., Zhu, Y., 2025. Multi-omics advances for molecular characterization, precision medicine, and prognostic implications in leukemia. Cell Investigation 1, 100007.

Hou, Y., Wang, X., Li, L., Fan, R., Chen, J., Zhu, T., Li, W., Jiang, Y., Mittal, N., Wu, W., et al., 2015. FHL2 regulates hematopoietic stem cell functions under stress conditions. Leukemia 29, 615-624.

Hua, W.K., Qi, J., Cai, Q., Carnahan, E., Ramirez, M.A., Li, L., Marcucci, G., Kuo, Y.H., 2017. HDAC8 regulates long-term hematopoietic stem cell Maintenance under stress by modulating p53 activity. Blood 130, 2619-2630.

Huang, P., Li, X.Y., Meng, Y., Yuan, B.H., Liu, T., Jiao, M.Y., Wang, X.D., Liu, Y.J., Yin, H., 2019. Interleukin-33 regulates hematopoietic stem cell regeneration after radiation injury. Stem Cell Res. Ther. 10, 123.

Jia, S., Laetitia, F., Ramine, M., Anne M.D., Erik, L., Loredana, S., Yongquan, C., Petervan, E., Birgitta, A., Julien, D., 2015. Pancreatic β-cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota. Immunity 43, 304-317.

Lefkopoulos, S., Polyzou, A., Derecka, M., Bergo, V., Clapes, T., Cauchy, P., Jerez-Longres, C., Onishi-Seebacher, M., Yin, N., Martagon-Calderon, N.A., et al., 2020. Repetitive elements trigger RIG-I-like receptor signaling that regulates the emergence of hematopoietic stem and progenitor cells. Immunity 53, 934-951.

Li, C.Z., Wu, B.H., Li, Y.S., Chen, J., Ye, Z.T., Tian, X.B., Wang, J., Xu, X., Pan, S., Zheng, Y.C., et al., 2022. Amino acid catabolism regulates hematopoietic stem cell proteostasis via a GCN2-eIF2α axis. Cell Stem Cell 29, 1119-1134.

Li, J., Kent, D.G., Godfrey, A.L., Manning, H., Nangalia, J., Aziz, A., Chen, E., Saeb-Parsy, K., Fink, J., Sneade, R., et al., 2014. JAK2V617F homozygosity drives a phenotypic switch in myeloproliferative neoplasms, but is insufficient to sustain disease. Blood 123, 3139-3151.

Li, Z. G., Fan, J.K., Xiao, Y.L., Wang, W., Zhen, C.L., Pan, J.B., Wu, W.R., Liu, Y.Y., Chen, Z., Yan, Q.R., et al., 2024. Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells. Leukemia 38, 2699-2708.

Li, Z.G., Fu, X.M., Wu, W.R., Liu, Z.L., Chen, Z., Zhou, C.F., Liu, Y.Y., Kuang, M., Sun, F.F., Xiao, F.F., et al., 2021. Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress. iScience 24, 102039.

Luo, Y., Song, Y.Z., 2021. Mechanism of antimicrobial peptides: antimicrobial, anti-Inflammatory and antibiofilm activities. Int. J. Mol. Sci. 22, 11401.

Marshall, N.M., Huanwen, C., Vendan, R.C., 2018. Constitutive activation of NF-κB pathway in hematopoietic stem cells causes loss of quiescence and deregulated transcription factor networks. Front. Cell Dev. Biol. 6, 143.

Mitchell, E., Chapman, M.S., Williams, N., Dawson, K.J., Mende, N., Calderbank, E.F., Jung, H., Mitchell, T., Coorens, T.H.H., Spencer, D.H., et al., 2022. Clonal dynamics of hematopoiesis across the human lifespan. Nature 606, 343-350.

Nakagawa, M.M., Thummar, K., Mandelbaum, J., Pasqualucci, L., Rathinam, C.V., 2015. Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence. J. Exp. Med. 212, 203-216.

Nakamura-Ishizu, A., Takizawa, H., Suda, T., 2014. The analysis, roles and regulation of quiescence in hematopoietic stem cells. Development 141, 4656-4666.

Nawaz, A., Shilikbay, T., Skariah, G., Ceman, S., 2022. Unwinding the roles of RNA helicase MOV10. Wiley Interdiscip. Rev. RNA. 13, e1682.

Qiu, K., Wang, X., Liu, Z., Peng, X., Zhong, S., Dai, Z., Zha, X., Wang, P., Zeng, C., 2025. Targeting USP10-FAK pathway sensitizes BCR-ABL+ leukemia cells to tyrosine kinase inhibitors. Cell Investigation 1, 100017.

Quaranta, P., Basso-Ricci, L., Hernandez, R.J., Pacini, G., Naldini, M.M., Barcella, M., Fin, L.S., Pais, G., Spinozzi, G., Benedicenti, F., et al., 2024. Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis. Blood 143, 1937-1952.

Schoggins, J.W., Wilson, S.J., Panis, M., Murphy, M.Y., Jones, C.T., Bieniasz, P., Rice, C.M., 2011. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472, 481-545.

Shen, C.H., Guo, Z.J., Liang, H.Y., Zhang, M.Z., 2023. Preliminary investigation of the immune activity of PmH2A-derived antimicrobial peptides from the pearl oyster. Fish. Shellfish. Immun. 135, 108691.

Simonnet, A.J., Nehme, J., Vaigot, P., Barroca, V., Leboulch, P., Tronik-Le Roux, D., 2009. Phenotypic and functional changes induced in hematopoietic stem/progenitor cells after gamma-ray radiation exposure. Stem Cells 27, 1400-1409.

Skariah, G., Seimetz, J., Norsworthy, M., Lannom, M.C., Kenny, P.J., Elrakhawy, M., Forsthoefel, C., Drnevich, J., Kalsotra, A., Ceman, S., 2017. Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain. BMC Biol. 15, 54.

Stepanchick, E., Wilson, A., Sulentic, A.M., Choi, K., Hueneman, K., Starczynowski, D.T., Chlon, T.M., 2024. DDX41 haploinsufficiency causes inefficient hematopoiesis under stress and cooperates with p53 mutations to cause hematologic malignancy. Leukemia 38, 1787-1798.

Strojny, W., Kwiecinska, K., Fijorek, K., Korostynski, M., Piechota, M., Balwierz, W., Skoczen, S., 2021. Comparison of blood pressure values and expression of genes associated with hypertension in children before and after hematopoietic cell transplantation. Sci. Rep. 11, 9303.

Sun, J., Furio, L., Mecheri, R., Van der does, A.M., Lundeberg, E., Saveanu, L., Chen, Y.Q., Van endert, P., Agerberth, B., Diana, J., 2015. Pancreatic β-Cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota. Immunity 43, 304-317.

Ulmke, P.A., Xie, Y.B., Sokpor, G., Pham, L., Shomroni, O., Berulava, T., Rosenbusch, J., Basu, U., Fischer, A., Nguyen, H.P., et al., 2021. Post-transcriptional regulation by the exosome complex is required for cell survival and forebrain development via repression of P53 signaling. Development 148, dev188276.

Umemoto, T., Hashimoto, M., Matsumura, T., Nakamura-Ishizu, A., Suda, T., 2018. Ca2+-mitochondria axis drives cell division in hematopoietic stem cells. J. Exp. Med. 215, 2097-2113.

Velardi, E., Tsai, J.J., Radtke, S., Cooper, K., Argyropoulos, K.V., Jae-Hung, S., Young, L.F., Lazrak, A., Smith, O.M., Lieberman, S., et al., 2018. Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury. Nat. Med. 130, 2619-2630.

Wang, N., Yin, J., You, N., Yang, S.D., Guo, D., Zhao, Y.Y., Ru, Y.X., Liu, X.Y., Cheng, H., Ren, Q., et al., 2021. TWIST1 preserves hematopoietic stem cell function via the CACNA1B/Ca2+/mitochondria axis. Blood 137, 2907-2919.

Wang, W., Snyder, N., Worth, A.J., Blair, I.A., Witze, E.S., 2015. Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production. Oncogenesis 4, e154.

Wei, Q.Z., Pinho, S., Dong, S.X., Pierce, H., Li, H.H., Nakahara, F., Xu, J.N., Xu, C.L., Boulais, P.E., Zhang, D.C., et al., 2021. MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of hematopoietic stem cells. Nat. Commun. 12, 2522.

Wu, W., Kim, C.H., Liu, R., Kucia, M., Marlicz, W., Greco, N., Ratajczak, J., Laughlin, M.J., Ratajczak, M.Z., 2012. The bone marrow-expressed antimicrobial cationic peptide LL-37 enhances the responsiveness of hematopoietic stem progenitor cells to an SDF-1 gradient and accelerates their engraftment after transplantation. Leukemia 26, 736-745.

Xiao, Y., Pan, J., Fan, J., Wang, W., Chen, S., et al., 2026. RNA helicase DDX21 sustains hematopoietic stem cell homeostasis by preventing nucleolar stress. Cell Investigation 2, 100060.

Xie, S.Z., Kaufmann, K.B., Wang, W., Chan-Seng-Yue, M., Dick, J.E., 2020. Sphingosine-1- phosphate receptor 3 potentiates inflammatory programs in normal and leukemia stem cells to promote differentiation. Blood Cancer Discov. 2, 32-53.

Yamashita, M., Passegue, E., 2019. TNF-α coordinates hematopoietic stem cell survival and myeloid regeneration. Cell stem cell 25, 357-372.

Yin, R., Chang, J.W., Li, Y.S., Gao, Z.Y., Qiu, Q., Wang, Q.F., Han, G.Q., Chai, J.H., Feng, M.D., Wang, P.P., et al., 2022. Differential m6A RNA landscapes across hematopoiesis reveal a role for IGF2BP2 in preserving hematopoietic stem cell function. Cell Stem Cell 29, 149-159.

Zhang, H.L., Zhang, X.D., Ling, C.X., Liu, C.E., Hua, S.D., Xiong, Z.Y., Zhao, H.M., Feng, Q.S., Feng, Z.C., Tang, J., et al., 2023a. EGFR-TNFR1 pathway in endothelial cell facilitates acute lung injury by NF-ΚB/MAPK-mediated inflammation and RIP3-dependent necroptosis. Int. Immunopharmacol. 117, 109902.

Zhang, Q., Ul Ain, Q., Schulz, C., Pircher, J., 2023b. Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation. Front. Immunol. 14, 1151926.

Zhao, J.W., Jia, Y.M., Mahmut, D., Deik, A.A., Jeanfavre, S., Clish, C.B., Sankaran, V.G., 2023. Human hematopoietic stem cell vulnerability to ferroptosis. Cell 186, 732-747.

Zhou, C.F., Kuang, M., Liu, Z.L., Jia, X.Q., Chen, Z., Liu, Y.N., Li, Z.G., Wu, W.R., Ma, L., Chen, J.P., et al., 2022. Insufficiency of FZR1 disturbs HSC quiescence by inhibiting ubiquitin-dependent degradation of RUNX1 in aplastic anemia. Leukemia 36, 834-846.

Zhou, C.F., Kuang, M., Tao, Y., Wang, J.M., Luo, Y., Fu, Y.H., Chen, Z., Liu, Y.Y., Li, Z.G., Wu, W.R., et al., 2024a. Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening. Cell Stem Cell 31, 1359-1375.

Zhou, Y.L., Zhao, M.Y., Gale, R.P., Jiang, H., Jiang, Q., Liu, L.X., Qin, J.Y., Cao, S.B., Lou, F., Xu, L.P., et al., 2024b. Mutations in DEAD/H-box helicase 11 correlate with increased relapse risk in adults with acute myeloid leukemia with normal cytogenetics. Leukemia 38, 223-225.

Relative Articles

Supplements(0)

Cited By

Proportional views