Gene expression in primary erythroid cells and in bone marrow stromal cells following treatment with Sotatercept (ACE-011)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41708 | GEO | 2012/10/20
SECONDARY ACCESSION(S): PRJNA178004
REPOSITORIES: GEO
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Project description:Gene expression in primary erythroid cells and in bone marrow stromal cells following treatment with Sotatercept (ACE-011) Gene expression profiles of erythroid cells derived from human CD34+ cells generated under standard conditions and in cultures containing conditioned media from bone marrow stromal cells treated in vitro with ACE-011; Gene expression profiles of untreated bone marrow stromal cells and of stromal cells treated with ACE-011.
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Project description:The non-hematopoietic cell fraction of the bone marrow (BM) is classically identified as CD45– Ter119– CD31– (herein referred to as triple-negative cells or TNCs). Although TNCs are believed to contain heterogeneous stromal cell populations, they remain poorly defined. Here we show, unexpectedly, that the vast majority of TNCs (~85%) have a hematopoietic rather than mesenchymal origin. Single cell RNA-sequencing reveals erythroid and lymphoid progenitor signatures among CD51– TNCs. When cultured with BM-derived stromal cells, Ly6D+ CD44+ CD51–TNCs give rise to B-lymphoid cells, whereas Ly6D–CD44+ CD51–TNCs generate erythroid cells. In addition, CD44+ CD51– TNCs contribute to repopulate B-lymphoid and erythroid cells after transplantation in mice. The CD44+ CD51– TNC population also expands during phenylhydrazine-induced acute hemolysis or in a model of sickle cell anemia. These findings thus uncover physiologically relevant, yet unappreciated, classes of stromal-associated CD45– hematopoietic progenitors.
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