Persistent DNA damage–induced NLRP12 improves hematopoietic stem cell function

• DOI: 10.1172/jci.insight.133365
• Publication Date: 2020-05-20T15:01:32Z
• Authors: Qiqi Lin; Limei Wu; Zhilin Ma; Fabliha Ahmed Cho...; Habibul Hasan Maz...; Wei Du
• Keywords: FANCA; Hematopoietic stem cell

NOD-like receptor 12 (NLRP12) is a member of the nucleotide-binding domain and leucine-rich repeat containing inflammasome family that plays central role in innate immunity. We previously showed DNA damage upregulated NLRP12 hematopoietic stem cells (HSCs) mice deficient repair gene Fanca. However, HSC maintenance not known. Here, we show persistent damage-induced improves function both mouse human models deficiency aging. Specifically, treatment Fanca-/- with cross-linker mitomycin C or ionizing radiation induces upregulation phenotypic HSCs. expression specifically induced by damage. Functionally, knockdown exacerbates repopulation defect Persistent was also observed HSCs from aged mice, depletion these compromised their self-renewal recovery. Consistently, overexpression substantially improved long-term repopulating Finally, maintains patients FA donors. These results reveal potentially novel suggest targeting has therapeutic potential disorders