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. |