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Publication : Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate.

First Author  Doi Y Year  2018
Journal  Cell Rep Volume  23
Issue  11 Pages  3223-3235
PubMed ID  29898394 Mgi Jnum  J:271094
Mgi Id  MGI:6278421 Doi  10.1016/j.celrep.2018.05.042
Citation  Doi Y, et al. (2018) Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate. Cell Rep 23(11):3223-3235
abstractText  Hematopoietic stem cells (HSCs) comprise a heterogeneous population exhibiting self-renewal and differentiation capabilities; however, the mechanisms involved in maintaining this heterogeneity remain unclear. Here, we show that SATB1 is involved in regulating HSC heterogeneity. Results in conditional Satb1-knockout mice revealed that SATB1 was important for the self-renewal and lymphopoiesis of adult HSCs. Additionally, HSCs from Satb1/Tomato-knockin reporter mice were classified based on SATB1/Tomato intensity, with transplantation experiments revealing stronger differentiation toward the lymphocytic lineage along with high SATB1 levels, whereas SATB1(-) HSCs followed the myeloid lineage in agreement with genome-wide transcription and cell culture studies. Importantly, SATB1(-) and SATB1(+) HSC populations were interconvertible upon transplantation, with SATB1(+) HSCs showing higher reconstituting and lymphopoietic potentials in primary recipients relative to SATB1(-) HSCs, whereas both HSCs exhibited equally efficient reconstituted lympho-hematopoiesis in secondary recipients. These results suggest that SATB1 levels regulate the maintenance of HSC multipotency, with variations contributing to HSC heterogeneity.
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