scholarly journals Universal signal generator for dynamic cell stimulation

Lab on a Chip ◽  
2017 ◽  
Vol 17 (13) ◽  
pp. 2218-2224 ◽  
Author(s):  
Andreas Piehler ◽  
Navid Ghorashian ◽  
Ce Zhang ◽  
Savaş Tay
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Gene Networks ◽  
Stem Cell Differentiation ◽  
Signal Generator ◽  
Cell Stimulation ◽  
Powerful Technique ◽  
Dynamic Cell

Dynamic cell stimulation is a powerful technique for probing gene networks and for applications in stem cell differentiation, immunomodulation and signaling.

scholarly journals INPP4B promotes leukemia by restricting leukemic stem cell differentiation through regulation of lysosomal functions

2021 ◽  
Author(s):  
John F. Woolley ◽  
Keyue Chen ◽  
Gizem E. Genc ◽  
Daniel K.C. Lee ◽  
Irakli Dzneladze ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Gene Networks ◽  
Stem Cell Differentiation ◽  
Leukemic Stem Cell ◽  
Lysosomal Function ◽  
Proteolytic Capacity ◽  
Lysosomal Gene

Despite an increased understanding of leukemogenesis, specific mechanisms that underlie stemness in leukemia remain largely undefined. Here, we report a novel pathway which regulates leukemic differentiation through control of lysosomal biology. We show that disruption of INPP4B results in dysregulated lysosomal gene networks, reduced lysosomal numbers and proteolytic capacity in leukemia. Inpp4b-deficient HSCs and LSCs are functionally compromised. Inpp4b-deficient leukemia models develop more differentiated leukemias with reduced disease initiating potential, and improved overall survival compared to Inpp4b-expressing leukemias. Together, our data is consistent with a model where INPP4B restricts differentiation of LSCs through regulation of lysosomal function. These data provide a mechanism to explain the association of INPP4B with aggressive AML and highlight avenues for LSC-specific leukemia therapies.

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