Expansion of Human Megakaryocyte-Lineage Progeny via Aryl Hydrocarbon Receptor Antagonism with CH223191

Dongchan Kim, Dong Yeop Shin, Jun Liu, Na rae Jeong, Youngil Koh, Junshik Hong, Xinxin Huang, Hal E. Broxmeyer, Sung Soo Yoon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aryl hydrocarbon receptor (AhR) antagonism is known to expand human hematopoietic stem cells (HSCs). However, its regulatory effect on the lineage-skewed differentiation of HSCs has not been sufficiently studied. Here, we investigate the effect of the AhR-selective antagonist CH223191 on the regulation of HSC differentiation. Consistent with the well-known effects of AhR antagonists, CH223191 treatment increase phenotypic HSCs (Lin-CD34 + CD38-CD90 + CD45RA-) and preserves their functionality. On the other hand, CH223191 leads to an overall expansion of megakaryocyte (MK)-lineage populations, such as MK progenitors (MKps, CD34 + CD41 +), immature MKs (CD41 + CD42b-), and mature MKs (CD41 + CD42b +), and it also activates MK/platelet-associated signaling pathways. Furthermore, CH223191 expands MKps, mature MKs, and p-selectin (CD62p)-positive platelet-like particles in immune thrombocytopenia (ITP) patient bone marrow (BM). These results highlight the numerical expansion of human MK-lineage progeny through AhR antagonism with CH223191. This approach using CH2231291 may be applicable in the development of auxiliary treatment regimens for patients with abnormal thrombopoiesis. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)2982-2994
Number of pages13
JournalStem Cell Reviews and Reports
Volume18
Issue number8
DOIs
StatePublished - Dec 2022

Keywords

  • Aryl Hydrocarbon Receptors (AhRs)
  • Cell Differentiation
  • Hematopoiesis
  • Hematopoietic Stem Cells (HSCs)
  • Immune Thrombocytopenia (ITP)
  • Megakaryocytes

Fingerprint

Dive into the research topics of 'Expansion of Human Megakaryocyte-Lineage Progeny via Aryl Hydrocarbon Receptor Antagonism with CH223191'. Together they form a unique fingerprint.

Cite this