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CDK8/19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes.
Br J Haematol
December 2024
Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Neonatal and adult megakaryocytes differ in proliferative capacity and ploidy levels, and neonatal and adult platelets differ in function, gene expression, and protein content. The mechanisms underlying these differences are incompletely understood. CDK8 and CDK19 are transcriptional kinases part of the CDK-mediator complex, which regulates gene transcription in a cell-specific manner.
View Article and Find Full Text PDFDifferent inflammatory, fibrotic, and immunologic signatures between pre-fibrotic and overt primary myelofibrosis.
Haematologica
October 2024
Departments of Medical Sciences; Departments of Cancer Evolution Research Center; Departments of Pathology, College of Medicine, The Catholic University of Korea, Seoul.
Primary myelofibrosis (PMF) is a myeloid proliferative neoplasm (MPN) characterized by bone marrow (BM) fibrosis. Pre-fibrotic PMF (pre-PMF) progresses to overt PMF. Megakaryocytes (MKs) play a primary role in PMF; however, the functions of MK subsets and those of other hematopoietic cells during PMF progression remain unclarified.
View Article and Find Full Text PDFPrevious studies of hematopoietic stem cells (HSCs) primarily focused on single cell-based niche models, yielding fruitful but conflicting findings . Here we report our investigation on the fetal liver (FL) as the primary fetal hematopoietic site using spatial transcriptomics. Our study reveals two distinct niches: the portal-vessel (PV) niche and the sinusoidal niche.
View Article and Find Full Text PDFGATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.
Adv Exp Med Biol
July 2024
Department of Pediatrics, Division of Hematology, University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
GATA1 is a highly conserved hematopoietic transcription factor (TF), essential for normal erythropoiesis and megakaryopoiesis, that encodes a full-length, predominant isoform and an amino (N) terminus-truncated isoform GATA1s. It is consistently expressed throughout megakaryocyte development and interacts with its target genes either independently or in association with binding partners such as FOG1 (friend of GATA1). While the N-terminus and zinc finger have classically been demonstrated to be necessary for the normal regulation of platelet-specific genes, murine models, cell-line studies, and human case reports indicate that the carboxy-terminal activation domain and zinc finger also play key roles in precisely controlling megakaryocyte growth, proliferation, and maturation.
View Article and Find Full Text PDFBRD9 regulates normal human hematopoietic stem cell function and lineage differentiation.
Cell Death Differ
July 2024
Dana-Farber Cancer Institute, Dept. of Medical Oncology, Boston, MA, 02215, USA.
Article Synopsis
- BRD9 is a protein involved in chromatin remodeling and has potential implications as a target for AML (acute myeloid leukemia), though its role in normal blood cell formation is not fully understood.
- Inhibition of BRD9 in hematopoietic stem and progenitor cells (HSPCs) results in decreased cell proliferation, loss of stem cells, and impaired differentiation into certain blood cell lineages.
- RNA sequencing indicates that BRD9 helps maintain active gene transcription during HSPC differentiation, particularly by regulating the master transcription factor GATA1, highlighting its role in the epigenetic regulation of blood cell development.
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