Bcl11a maintains hematopoietic stem cell function but accelerates inflammation-driven exhaustion during aging.

Jing Wang, Linlin Zhang, Xinyu Cui, Xiang Xu, Rui Guo, Kairui Li, Li Zhang, Bing Xu, Cizhong Jiang, Yong Yu

Department of Hematology, Tongji Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.Department of Hematology, Tongji Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. · pubmed

Paper

Abstract

Preserving hematopoietic stem cell (HSC) functionality is essential for maintaining healthy blood and the immune system throughout life. HSC function declines with age; however, the underlying mechanisms are not fully understood. Using an inducible mosaic mouse model to overexpress the transcription factor Bcl11a in the hematopoietic compartment, we found that an aging-related increase in Bcl11a mitigated HSC functional decline, promoted IL-1β production in the bone marrow (BM), and accelerated HSC attrition in a non-cell-autonomous manner. Aging-related inflammation in the BM enhanced Bcl11a and Fc receptor (FcR) expression in HSCs, and FcR signaling induced HSC differentiation. This was counteracted by Bcl11a through repression of

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Research summary

The paper claims that increased Bcl11a expression mitigates hematopoietic stem cell functional decline during aging but accelerates inflammation-driven exhaustion. This research is relevant as it explores mechanisms underlying the decline of stem cell function with age, which is a critical aspect of aging and longevity.

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