Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia
- Iskander, D.
- Wang,G.
- Heuston, E.F.
- Christodoulidou, C.
- Psaila, B.
- Ponnusamy, K.
- Ren, H.
- Mokhtari, Z.
- Robinson, M.
- Chaidos, A.
- Trivedi, P.
- Trasanidis, N.
- Katsarou, A.
- Szydlo, R.
- NISC Comparative Sequencing Program
- Palii, C.G.
- Ziadi, Z.
- Al-Oqaily, Q.
- Caputo Galarce, V.
- Roy, A.
- Harrington, Y.
- Karnik, L.
- Naresh, K.
- Mead,A.J.
- Thongjuea, S.
- Brand, M.
- de la Fuente, J.
- Bodine, D.M.
- Roberts,I.
- Karadimitris, A.
- Iskander, D.
- Wang,G.
- Heuston, E.F.
- Christodoulidou, C.
- Psaila, B.
- Ponnusamy, K.
- Ren, H.
- Mokhtari, Z.
- Robinson, M.
- Chaidos, A.
- Trivedi, P.
- Trasanidis, N.
- Katsarou, A.
- Szydlo, R.
- NISC Comparative Sequencing Program
- Palii, C.G.
- Ziadi, Z.
- Al-Oqaily, Q.
- Caputo Galarce, V.
- Roy, A.
- Harrington, Y.
- Karnik, L.
- Naresh, K.
- Mead,A.J.
- Thongjuea, S.
- Brand, M.
- de la Fuente, J.
- Bodine, D.M.
- Roberts,I.
- Karadimitris, A.
DOIAbstract
Ribosome dysfunction underlies the pathogenesis of many cancers and heritable ribosomopathies. Here, we investigate how mutations in either ribosomal protein large (RPL) or ribosomal protein small (RPS) subunit genes selectively affect erythroid progenitor development and clinical phenotypes in Diamond-Blackfan anemia (DBA), a rare ribosomopathy with limited therapeutic options. Using single-cell assays of patient-derived bone marrow, we delineated two distinct cellular trajectories segregating with ribosomal protein genotypes. Almost complete loss of erythroid specification was observed in RPS-DBA. In contrast, we observed relative preservation of qualitatively abnormal erythroid progenitors and precursors in RPL-DBA. Although both DBA gen...
Add to ORKG